APPROPRIATE TECHNOLOGIES

FOR DOUBLE FORTIFICATION OF SALT

RIZWAN YUSUFALI

A thesis submitted in conforrnity with the requirements

for the Degree of Master of Applied Science

Graduate Department of Chernical Engineering and Applied Chemistry

University of Toronto

Q Copyright by Rizwan Yusufali 200 1

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APPROPRIATE TECHNOLOGIES

FOR DOUBLE FORTIFICATION OF SALT

BY

RIZWAN YUSUFALI

A thesis submitted in conformity with the requirements

for the Degree of Master of Applied Science

Graduate Department of Chernical Engineering and Applied Chernistry

University of Toronto

Q Copyright by Rizwan Yusufali 2001

ABSTRACT

Techniques for double fortification of salt with iodine and iron suitable for

implementation into developing countries were investigated. The technology's

simplicity, cost efficiency and versatility will be important. The basic premise of the

work was that encapsulation will protect iodine and iron frorn reactions with each other

and with moisture and irnpunties that are normally present in the salt.

Cocrystallization and agglornention followed by encapsulation were employed in

producing premix particles. With cocrystallization there was little control of iodine

content, particle size, and reproducibility. Agglomeration yielded positive results and

premix particles of sirnilar size to that of salt with required iodine and iron content, and

acceptable colour were achieved. Pilot scale studies on agglomeration were performed

successfull y.

The best formulation for double fortification retained more than 90% iodine over 3

months at 40°C and 100%RH. The stable formulations consisted of potassium iodide or

iodate dispersed within a dextrin rnatrix and encapsulated with soy stearine or polyrnethyl

methacrylate. As little as 20% soy stearine and 6% polymethyl methacrylate

encapsulation level were found to be sufficient.

ACKNOWLEDGEMENTS

1 would like to convey my sincerest gratitude to Professor Levente L. Diosady for his

guidance and kind advice during this project and for giving me the opportunity to work

on a cause that may improve the lives of countless people around the world.

My thanks also go to Joseph Alberti for his support, Professor Ron Hancock for his help

with NAA, Paul Jowlabar, Susan Abel at Weetabix and Peter Ozols at Guelph Food and

Technology Centre for their help with pilot scale tests.

I cannot forget my fnends Francesca A p m e s e , Bih King Chen, Dr. Lei Xu, Ildiko

Railleanu, Iftikhar Turi, David Balke, Anne-Sophie Parazols and the entire Food

Engineering group for their input, moral support and invaluable friendship.

Lastly and certainly not in the least, I would like to thank my parents, my wife Insiya and

the rest of my family for offering their kind words of encouragement, undying support

and patience. 1 could not have done anything without you.

TABLE OF CONTENTS

ABSTRACT ................................................................................................................................. I I

ACKNOWLEDGEMENTS ............................................................................................... I I I

TABLE OF CONTENTS ............................ ......, ....................................................... IV

L I OF F U S ......................................................................................................... VI

LIST OF TABLES ...................................................................................................................... IX

1. INTRODUCTION ......................,....................................*......*....,............................................. i

2. THEOFUTICAL BACKGROUND .... ........ .............. .......... ... . . . . . 6

2. I IODlNE AND IRON DEFICIENCY DISORDERS ................................................................................... 6 2.1. I lodine Deficiency 6

2.2 CHEMISTRY OF IRON AND IODINE ............................................................................................... f 0 2.3 SELECTION OF A VEHICLE AND FORTINING COMPOUNDS .................................. .., .................. 14

7.3.1 Choice And Dosage Of Iodine Compound 16

2.3.7 Selection .4nd Dosage Of Iron Compound 19

2.4.2 Approaching The Design Of Size Enlargement Processes 28

2.4.3 Size En largement Equiprnrnt And Practice 30

2.5 ENCAPSULATION ....................................................................................................................... 36 2.5 1 Choice Of Encapsu lant 37

2.52 Surface Characreristics Of Films 39

2.5.3 Solvent SeIection 40

3.1 MATERIALS ....................................................................................................................................... 42 3.2 EQUIPMEM .......................... - .............................................................................................. 42 3.3 EXPERIMEMAL PROCEDURE ........................................................................................................... 44

3.3.1 Pan Aggiomeration 44

3.3.2 Spray Cooting 44

3.3.3 Spray Drying 45

3.4 A N A L ~ C A L METHODS ......................................................................................................... 46 3.4.1 Moisture Content 46

3 .42 Iodine Anafysrj 47

3.4.3 lron .Jnu/ysis

3.4.4 Particle Si=e Distribution

3.5 SAMPLE S T O U G E AND PACLIGMG ............................................................................................... 49

3. RESULTS AND DISCUSSION ............................................................................ so 4 . 1 CO-CRY STALLIZ.~TION. .................. . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . -........... . . . . . 5 1 4 2 AGGLOMERATION AND SlZE ENLARGEMENT ..................................................... . .............. . . . . 56 4.3 OPTIMIZATION OF PREMIX FORMULATIONS ............................................................................. 62

-1.3.1 Eflect Of Storage Conditions On Iodine Retention 63

4.3.2 Effect of Adàition of SHMP Stabilizer on Iodine Retention 6 J

4.3.3 Eflect of Qpe of lron on Iodine Retention 63

4 . 4 SELECTION OF OPTIMAL ENCAPSULATING AGENTS ............................................................................ 69 4.5 OFTIMIZATION OF ENCAPSULATION LEVEL AND FORMULATION ...... .... ... .............................. 7 1

4.5.1 1odine Retention 73

4.5.2 fron Conversion 74

4.5.3 Colour Change In Double Fortifed Salt 75

5. CONCLUSIONS ................................................................................................................... 93

6. RECOMMENDATIONS ................................................................................................ 94

7. REFERENCES .................................................................................................................. 96

8. NOMENCLATURE ..................................................................................................... 103

9. APPENDICES .................................................................................................................... 1 OJ

9.1 EXPEUMENTAL RESULTS ................................................................................................................. IO4 9.1.1 Summury ofresults of shellac encrrpsuluted batches 10-4

9.1.2 Surnmary ofresults of Zein Encapszdated Batches 1 05

9.1.3 Surnmary of shellac encapsulated Km3 premix batches srored at d~flerent conditions, different iron sources. und with or without stabilizers. 106

9.1.4 Resulrs ofscreening fesis for dtf/erent encapsulanfs 107

9.1.5 Summary of results of experimental mns/or optimization of encapsu fation level and vpe ofencapsulant, iron source unci iodine source 1 08

92 SAMPLE CALCULAT~ONS .......................................................................................... . ................ . 1 12 9.2.1 Iodate A nulysis II2

LIST OF FIGURES

Figure 2. ka ) Thyroxine (3.5.3 : 5 '-tetraiodothyronine{TJ)): b) 3.53 'triiodothy'onine (T3)

Figure 2.7: Salr fortified rvith ferrous sulphare heptahydrate ujer exposure to 100% humidity and -(O"C over 3 tnorrths. ferrous srilphare (le#), encoprlared ferrous srdphate (right)

Figure 2.3: Cross secrional view of an ideal encupsulated par ficle

Figure 7.4: The rate processes of agitative agglot~rernrion. which inclide powckr wetiing. granule growth, granule consolidation and granule attrition.

Figure 2.5: Cirt-out view of a Wurster Process Chatnber

Figure 2.6: Spruy Dryer

Figure 3.1: Diagram of rotating pan used for agglomeration and spruy couring of particles.

Figrire 3.2: Flow diagrarn of a typical cocrystullizarion procehrc?

Figrire 3.3: ,.1 Ru- Tap sieve shaker with a stock of sieves

Figure 4.1: Diagram illustraring bonding and attrition of HOi and NaCl crystais

Figure 4.2: Slability of sheliuc encupsulated KIOJ pretr~ix usedfor Joiible fortijkation of salt with ferro us fimarate

Figiirr 4.3: Stability ojzein encapszrlated HO3 prentix irsedfor clodde fortificotiorr of sait wirh ferro us fimarute

Figure 4.4: Iodine retention 13% shellac-encapsulated KlOJ barches, single and double fortified withjerrous suiphate and stored under room conditions and 4U"C-1 O O % R H

Figure 4.5: Comparison of iodine retention in batchcs contairiing 13% shelluc- encapsulated KlOJ premix and ferrous sulphate wilti dlflerent aniounts of SHMP

Figure 4.6: Comparison of iodine retention benveen single fortified sali and double fortified salt with ferrous fumarate and ferrous sulphate respectiveiy, srored under JO"C and I O O % R H - iodine source -1 3% shellac encapsulated KIOJ premix

Figure 1.7: Iodine retention of double fort@ed batches with Kï03 premix encapsulated by d~rerent encapsulan fs and unencapsulatedjërrous fimarute

Figure 4.8: Iodine retention of double fortified batches with HO3 premix encapsulated by dlrerent encapsulants and encapsulated ferrous fimurate

Figure 4.9: .Retention of iodine in batches double fortiped with soy stearine encapsulated HO3 premk and soy stearine encapsuiated ferrous fimarate premix d e r 3 months of storage at JO"C und 1 OO%RH.

Fipire 4.10: Conversion of ferrot iron to ferric iron in barches dotible fortified rvith soy stearine encapsulated Kiû3 premiic and soy srearine encapstrlared ferrous fimurate premk after 3 months of storage ut 4O"C und 1OO%RH.

Figure 4. / I : Appearance of double forrijied salt samples aper 3 months of srorage under #O"C crnd 100% RH.

Figure 4. II: Retention of iodine in batches double forfified with soy stearine encapszdated KIOJ prenrix and soy stearine encapsirlated ferroils sulphute premir aJer 3 mortrhs of srorage ut 4O"C and 1 OO%M

Figure 4.13: Conversion of ferrous iron io ferric irori in barches double forrifiedivirh soy stearine encapsulated K/OJ prerrtir und soy sreurine encupsdated ferrous siilphare prernir a)er 3 rnonrhs of storage ar 4O"C and I OO%RH. 75

Figure 4.14: Appearance of double fort fted salt samples afrer 3 ntonths of srorage trnder 4O"C and 100% RH. 79

Figure 4.15: Retention of iodine in batches double forrified wirh polyntethyl niethacrylare encapsulared KIOJ prenrir and soy srearine encapsulared ferrous fiimarate prernix afrer 3 monrhs of srorage ar 4O"C and I O O % R H . 80

Figure 4.16: Conversion of ferrous iron io ferric iron in barches double forrrjied wirh polymer~l methactylare encapsulared WOJ premix and soy stearine encapsuZaied ferrous fumarate premi-r afrer 3 moriths of storage ar 30°C und 1 OO%RH.

Figzire 4.17: Appearance of double forrified salt samples afrer 3 months of storage under 4O"C and 100% RH.

Figzrre 4.18: Retention of iodine in barches double forrijied wirh polyniethyl methacr/klte encapsdated HO3 premk und soy stearine encapstilured ferrous sulphate prernix afier 3 rnonrhc of storage ur 4VC and 1 OO%RH. 82

Figure 4 19: Conversion of ferrous iron to ferric iron in batches double forti/ied wirh polymethyl merhacrylare encapsulated KlOJ premix and soy stearine encapsulated ferrous sulphate premix aifer 3 monrhs of srorage ai J#C and I OO%RH. 82

Figure 4.20: Appearcmce of double fortified salr samples a$er 3 months of storage under JO"C and 100% RH. 83

Figure 421: Retention of iodine in batches doublefortl/ied with soy sreurine encapsulated Hpremix and soy stearine e~cap~u~asedferrous fimarate premix aftet 3 months of storage ut JVC and I OO%RH. 84

Figure 4.22: Conversion of ferrous iron IO femic iron in balches double fortijiede with soy stearîne encapsdated KI prrmir and soy stemine encapdated /errousfimarate premir d e r 3 month of storage ut 4VC and 1 OO%RH.

Figure 4.23: Appearance of doublejortified salt samples ufier 3 month of s~orage under 40°C and 100% RH.

vii

Figure X 24: Retention of iodine in batclies double fortrfied wirh soy srrarine encnpsz duted KI premix m d soy srearine encapsu la1 ed ferrom suiphrire pretnir afrer 3 months of storage at M C and I OO%RH.

Figure 4.25: Conversion of ferrous iron ro ferric iron in batches dozrbIeJorr$ed wirh soy srearine encapsulated KI premir und soy stearirie encopsztIated ferrous szrlphare premk afrer 3 rnonrhs of storage at 4O"C and I OO%M

Figzrre 4.26: Appearance of double fort9ed saif samples ajler 3 monrhs of storage zrnder N C and 100% RH.

Figure 4.27: Relention of iodine in batches double forrified rvith polyniethyl merhacrylare encapsulated Kl preniir and soy srearine encapsulated ferrous fimarate premix ajler 3 month of srorage a[ 4O"C and I OO%RH.

Figure 4.28: Conversion of ferrola iron to ferric iron in barches double forr~jied with poiymerItyln~erhacryIate encapsulared KI prenlir and soy stearine encapsulated ferrous fumarate premir afier 3 nionths of storage at 4#'C und I OO%RH.

Figure 4.29: Appearance of double fort~jied sait samples afer 3 rnonths of sroruge under 4O"C and 100% RH.

Figzrrr 4. JO: Rereniiori of iodine in barches double for~ijied rvith po lynlerhyl ethacrylate encapsulated K i premix and soy srearine encapslrlared errozlr szdphate premk after 3 monrhr of sforage al 4 ü î and I OO%RH.

Figure 4.3 1: Conversion of ferrous iron ro fenic iron in batches double forri/ied ivitlr polyntethylmerhacry late encapsulated KI premir and soy stearine encopsulated ferrous sulphare premir afier 3 months of storage ar 4û"C cind I OO%RH.

Figiire 4.32: .4ppearance of double fortifie J sait satnples afer 3 month of srorage under 4O"C and 100% RH.

LIST OF TABLES

Table 2.1:

Table 2.2:

Table 2.3:

Table 2.4:

Table 2.5:

Table 3. Ir

Table 3.2:

Table 4.1:

Table 4.2:

Table 4.3:

Tuble 4.4:

Table 4.5:

Tuble 4.6:

Table 4.7:

Absorbe J iron requirenrents (nzg/clay) ar d~jiereni sruges of the hirmun lye cycle

Physical propert ies of iodine and ifs conipo~rnds

Salt iodizat ion leve ls in selecred CO unrries

Comnrrrciai~v available ironfcirt~ficunts und iheir e_Oecriveness und i m character ist ics

Properries of selected encapstrlating agen rs

List of chernicals used

Operating condirions for pilot scaje spray drying mrs.

Coniparison of Traditional Forrificarion Vs. The Prent ir A pproach

Sunmn~ary of resrtlis ofco-crysrallizarian batches

Variation in iodine content betweens samples and befiveen replicure analyses runs.

Summury of restilrs of caking rrrns

Operut h g purumerers for 1 kg pi10 i scale agg20t)trrarion rtrn

Operuring purorneters for 5 kg pif or scule ugglonieration rtrn

Combimions sr iidied for oprin~izurion of prem ix formitlarion und encapsularion level

1. INTRODUCTION

In recent years there has been an increased global awareness of micronutrient

deficiencies. Iron and iodine deficiencies in particular have the largest detrimental effect

on human health and well-being. lron and iodine deficiency collectively impacts over 2

billion people around the world. Food fortification is an efficient way of combating these

problems.

lnsufficient intake of iodine in the diet causes cretinisrn. deaf mutism, goitre, leads to

stunted growth, miscmiages. as well as infant and neonatal mortality. These diseases

collectively known as lodine Deficiency Disordes (IDD) c m be easily prevented by

consumption of adequate arnounts of iodine. The average daily requirement of iodine is

about 150 pg (Merck Manual, 1997)

The speciai biological importance of iodine ax-ises frorn the fact that it is a constituent of

the thyroid hormones thyroxine (3.5,Y.j'-tetraiodothyronine(T4)) and 33.3 . -

hiiodothyronine(T3). Both these hormones play a role in controlling the body%

metabolism. In children these hormones are also essential for normal physical growth

and mental develo pment.

Iodine occurs most abundantly in nature in oceans. It was present during the primordial

development of the earth, but large amounts were leached from the surface soi1 by

glaciation, snow, and rain, and were canied by wind and ninning water into the sea. As a

result. highland populations tend to be more iodine deficient and generally have higher

occurrences of IDD.

Iron deficiency (ID) is the most common nutritional disorder in the developing world and

the most common cause of nuvitional anaemia in young children and women of

reproductive age. The economic and social consequences of iron deficiency are

enormous. Lack of suficient iron in the diet can lead to anaemia which in turn Ieads to

increased matemal mortality, foetal growth retardation, prenatal and postnatal monality,

reduced development of motor skills and learning capacity, lowered physical activity and

reduced immunity to diseases.

About one third of the body iron is storage iron (existing as femtin and haemosiderin).

The rest of the body's iron is functional. existing mainly as haernoglobin in blood.

myoglobin in muscles and lesser amounts in iron containing enzymes. Iron deficiency

develops only when storage iron is depleted and there is insufficient iron absorption to

counteract the amount lost fiom the body through faeces, desquamated mucosal and skin

cells, and rnenstrual blood loss among women.

Iron deficiency is harder to combat as imn status is associated less with intake and

depends more on the bioavaîlability of the consumed iron. The presence of iron

absorption inhibitors or enhancers can also alter the d d y iron requirement.

Iron deficiency has in the past tended to suffer relative neglect as a micronutrient

deficiency. In the last decade an improved understanding of the detrimental

consequences of iron deficiency and increased success of global iodine fortification has

led to a more concertrd action to provide iron in the diet.

With the success of global iodization programs and the "doability" of providing

micronutnents through a vehicle such as salt, a more focussed prognm was developed to

provide both iron and iodine in normal table salt. Salt has proven to be an ideal vehiclc

for combating rnicronutrient deficiencies especially in the developing countries because it

is cheap, its consumption is generally uniform throughout the population strata and is not

dependent on socio-economic status, and it has low potential for excessive intake.

This research focuses on overcoming the problems associated with double fortification

(DF) of salt with iodine and iron and at the same time developing a suitabie technique for

double fortification which is relatively simple and cheap to implernent.

Adding iron and iodine concurrently to salt is not without its own challenges. The fact

that salt in most developing countries is highly impure poses a problem for its double

fortification with iodine and iron. Iron is normally added as its ferrous (Fw) form and

this can be easily oxidized to the femc (Fe+++) Form which is less bioavailable and

usually imparts a metailic taste and a brownish red colour to the salt. Iodine on the other

hand is normally added either as its iodide or iodate compound and can be easily

converted to its elemental state (12) through reduction or oxidation and in the presence of

high humidity and sunlight. The fiee iodine sublimes and evaporates easily into the

atmosphere and is no longer present in the diet. In addition having iodate and iron(I1)

present at the same time can trigger a redox reaction when the two are in contact to

release iodine and convert iron(I1) to iron(II1).

Several research groups have focussed on increasing the stability of double fortified salt

through the addition of stabilizing agents (Narasinga Rao, 1975) and through better

packaging of salt (Diosady, 1998). These approaches have yielded some mixed results.

A more feasible approach seems to be that which physically protects the active

ingredirnts from adverse effects. Diosady and Alberti proved that encapsulating

potassium iodine within a dextnn matrix through spny drying produced a stable salt with

negligible iodine losses. This project is a follow-up on the idea of isolating the active

ingredients and hence eliminating contact with impurities md moisture.

Although spny drying yielded good results, a technique for producing a similar product

that was less expensive. more versatile and yielded the desired size was needed. In this

project several methods were investigated of agglomerating and microencapsulating the

iodised and iron fortified particles. This premix was more concentrated with the

micronutrients and thus it could be easily mixed with locally available salt to obtain the

desired dose.

Another important aspect of this study was to optimise the formulation of the premix.

Several binding agents for agglorneration, fillers to alter dosage and encapsulants to form

the physical b h e r were tested for their suitability.

The stability of al1 the batches was monitored for three months under 40°C and 100%

relative hurnidity for loss of iodine and conversion of iron. These conditions are the

worst encountered by salt during storage, transportation and distribution. Batches that

showed good stability also undenvent bioavailability studies for iron.

Pan granulation or agglomeration was found to be a feasible method and pilot scale

studies of up to jkg were performed to see if the process could be scaled up to produced

larger amounts of premix.

2. THEORETICAL BACKGROUND

2.1 Iodine And Iron Deficiency Disorders

Healthy humans require iodine, an essential component of thyroxine and

trîiodothyronine. Inadequate consumption of iodine leads to insufficient production of

these hormones, which affect many parts of the body. particularly muscle, hem, Iiver.

kidney and the developing brain. The healthy human adult body contains 15-15 mg of

iodine of which 70-80 percent is in the thyroid gland. The normal iodine intake is about

100-150 pg per day, of which the thyroid has to trap about 60 pg per day to maintain

adequate thyroxine supply.

The basic effect of iodine deficiency is to interfere with the production of thyroid

hormones. because iodine is an essential constituent of the TJ and T3 molecules.

Inadequate hormone production leads to the disease States collectively known as the

iodine deficiency disorders. or IDD. These consequences include mental retardation,

defects in the development of the nervous system, goitre (enlarged thyroid), physical

sluggishness, growth retardation, reproductive failure, increased childhood mortality, and

ultimately leads to economic stagnation.

Iodine deficiency has been called the world's majsr cause of preventable mental

retardation. Its severity c m Vary from mild intellectual blunting to frank cretinism, a

condition that includes gross mental retardation, deaf mutism, short stature, and various

other defects.

Insufficient iodine intake triggen the release of the hormone TSH. which in turn signals

the thyroid gland to increase the uptake of iodine from the blood Stream. If the diet Iacks

iodine for an rxtended period, the cells of the thyroid gland swell causinç the thyroid

gland to enlarge, a condition more commonly known as goitre.

Consumption of too much iodine can also lead to goitre. This condition is known as

hyperthyroidism. Hyperthyroidism does occur is a small fraction of individuals who are

deficient in iodine and are suddenly exposed to high doses of iodine. The thyroid in this

case is overactive.

Universal Salt Iodisation (USI) does put a small fraction of the population at risk through

hyperthyroidisrn and may not benefit people who are on low sodium diets or avoid salt

consumption. However, the number of people whose lives c m be improved makes these

problems insignificant.

2.1.2 Iron Deficiency

Nutritional iron deficiency is a major problem in developing countries. The only proven

way it can be elirninated is through increasing the iron intake. This can either be done by

providing medicinal iron (supplementation) or by adding iron to the diet (fortification).

Fortification has been proven to be more efficient, especially because it is less expensive,

does not require highly paid professionals to dispense and administer dosage, and if put

in foods such as salt, virtually eliminates risks of overdose.

Iron in the hurnan body c m be classified into two categories, functional iron (mostly as

haemoglobin in the blood and myoglobin in the muscles) and, storage iron (as ferritin and

haemosiderin). Iron deficierky develops when the storage iron is depleted and the

consurnption is inadequate to cover the loss. If the loss of stonge iron continues

functional iron may become depleted and this leads to iron deficiency anaemia. Iron c m

be lost from the body through menstnial blood loss, blood in the faeces (usually onset by

a digestive tract disease and parasites), and desqumated inucosal and skin cells.

(Clydesdale et al. 1985)

Iron deficiency is harder to combat than sorne of the other nutrient deficiencies due to the

fact that the iron requirement is different for individuals of different age and gender. Iron

deficiency is associated with the actual amount of iron absorbed that may not depend on

the amount of iron consumed. The presence of iron absorption enhancers (such as

vitamin C, and chromium) or inhibiton (such as nicotine, phytic acid and other chelating

agents) can alter the amount of iron available. (Fornon et al. 1992)

In our study we aim to supplement the diet by adding about a third of the daily iron

requirement to salt. This decision was based on the assurnption that many other food

sources also contain iron. Iron absorption in the body occurs almost entirely in the

duodenurn, which makes up about 7 cm of the whole digestive tract. Normally o d y a

quarter of the available iron is actually absorbed by the hurnan body. The table below

lists the daily absorbed iron requirernent for humans at different stages of theirs Iives. It

should be noted that pregnant women have much higher iron demands and in this case

fortification programs are generally not enough. Extra iron supplementation during

pregnancy would be essential.

1 Age and physiological group 1 ivedian absorbed iron requirement - - -

4- 1 1 month infants 1 0.96 1 12-23 rnonth preschool children 24-59 month preschool children 6- 1 1 yr schoolchildren 12-1 6yr adolescent girIs

0.6 1 0.70 1.17 3.02

12-16yr adolescent boys Adult men Non-pregnant wornen

1.82 1.14 2.3 8 . -

Pregnant women ( 1 " trimester) Pregnant women (20a trimester)

-

Table 2.1: Absorbed iron requirements (mg/day) at diifment stages of the human life cycle

Source: FAO/WHO 1988

1 6 (largely blood expansion) -

Pregnant women (3" trimester) ' 1 O ( l a ~ ~ l y j i x t a l &wh)

When the iron stores in the body are depleted and insufficient iron is consumed to

counteract the loss, iron deficiency anaernia occurs. Iron is essential for the oxygen

transport by haemoglobin and myoglobin, as well as being a component of many

enzymes which are required for the adequate fùnctioning of brain cells, muscle cells, and

the cells of the immune system. Lack of sufficient iron can lead to increased matemal

mortality, increased risk of foetal growth retardation, prenatal and postnatal mortality,

cornpromised development of motor skills and learning capacity, growth failure, poor

physical developmeni , lowered physical activity (Iethargy), and decreased immunity to

disease. (Gillespie, 1996)

Lactating women Post-meno~ausal women

1.3 1 0.96

2.2 Chemistry Of Iron And Iodine

Iodine (12) is a dark violet non-metallic element, belonging to group VI1 in the periodic

table. It is insoluble in water but soluble in ethanol and many other organic solvents.

Iodine is required as a trace elemeni by living organisms; in animals it is concenuated in

the thyroid gland as a constituent of the thyroid hormones thyroxine (3,5.3',5'-

tetraiodothyronim(T4)) and. 3,5,3'-triiodothyronine (T3).

a) TETUIODOTHYRONINE (THYROXINE)

Figure 2.1 a) Thyroxine (3$,3',5'-tetraiodotby ronine(T4)); b) 333'-triiodothyronine (T3)

In fortification of food, iodine is usually introduced as the iodide or iodate of potassium,

calcium or sodium. In salt iodization, potassium iodate is found to be more stable than its

iodide counterpart in the presence of high humidity and moisture, and is therefore the

cornpound of choice in developing countries where salt has higher moisture. (Venkatesh

Mannar, Dunn, 1995). Potassium iodide is used most frequently in developed countries

with refined salt. The criteria for selection of iodine and iron compounds are discussed in

more detail as a separate section in this thesis. Iodide oxidation and iodate reduction

genenlly leads to the formation of volatile iodine:

21' -+ I2 + 2e' (oxidation)

21'' + I Oe' -, I2 (reduction)

The rate of oxidation of iodide to volatile iodine depends on pH and concentration of

iodide. It has been found that the partitioning ratio of free iodine species in air increases

with decreasing pH and decreasing iodide concentration (Evans et a1.1993). It is also

widely accrpted that iodide oxidation can also be catalyzed by high temperature. sunlight.

and the presence of moisture and trace metal impurities.

Salt in most developing countries contains high levels of impurities, is poorly stored and

distributed, and in some cases the surface temperature of salt stored in humid sheds or

under sunlight can be as high as 80°C. Al1 these conditions favour the conversion of

iodide or iodate salts into fiee iodine. Solar sea salt in most developing corntries also

contains magnesium and calcium chlorides as impurities, hydrolysis of these salts in

water produces an acid:

MgCh Mg(0H)CI + HCl (2) (*similarly with Ca")

(3) (*similarly with Ca")

The resultant acid facilitates the decornposition of iodide or iodate as follows when

sunlight and oxygen are present:

At elevated temperature, the reaction proceeds as follows:

The research on stable iodized salt has been prirnarily based upon elirninating conditions

that promote the formation of volatile iodine species. The focus has been on improving

the quality of salt to reduce impurities. addition of basic stabilizing agents, since at higher

pH the decomposition of iodide or iodate is greatly reduced (Venkatesh Mannar 1995.

Narasingha Rao 1994, Evans 1993), improving the packaging of fortified salt (Diosady et

al. 1998), addition of reducing agents such as dextrose (Diosady et al. 1998) and

dehydnting free flowing agents such as calcium silicate. and encapsulation of iodine.

The addition of iron to iodized salt, in essence double fortification, poses fùrther

challenges to fortification. The most important oxidation states of iron are +2 and +3.

though coordination complexes with +4 and +6 states are also known. Ferrous ( ~ e " )

compounds are usually pale green due to the ~ e " ion or complex ions. Ferric compounds

are usually yellow, orange or brown, depending on the extent of hydrolysis. Ferrous iron

is usually used in food fortification due to its higher bioavailability. Through oxidation,

the ferrous form can be easily converted to its femc form which is less bioavailable and

darker in colour:

Fe* (green) --b FeM(orange/red) + e-

This reaction is more likely to occur under acidic conditions or in the presence of an

oxidizing agent, but it rnay also occur through air oxidation at a Iow pH. The rate at

which iron oxidation occurs is largely dependant on the nature of the food and the

conditions under which it is stored. Trivalent iron salts react with iodide to produce free

iodine which escapes easily:

The reduction of iodate cm be accelerated by the presence of ferrous salts. A redox

reaction between ~ e " and 1" occurs very easily to yield volatile iodine and oxidation of

ferrous to femc:

These reactions occur in aqueous systems. This means that moishm needs to be present

for the reaction to proceed and results in this study confirm that at higher moisture levels

the loss of iodine and the conversion of ferrous iron to femc iron is indeed accelerated.

Eliminating rnoisture has proven to be an effective method to increase the stability of

double fortified salt. In the past the approach has been to eliminate moisture through

better salt packaging. This option is however not feasible in many developing countries

as it would greaatly increase the price of salt. Other solutions such as puriQing salt,

adding stabilizers and chelating agents would also increase the pnce of salt and make it

unaf5ordable to the targeted population.

A possible alternative to producing double Fortified salt which is stable for longer

periods, i.s. at Irast 6 months, would be to encapsulate the active ingredient with a water

insoluble shell and hence isolate the active ingredient from moisture, trace metals, and

other impunties. This method would also increase the price of the salt, but if the

technology were made simple enough, the impact on cost would be minimal.

Administering iron in non-food systems would be much more expensive in cornparison.

A concentrated premix approach would also greatly reduce the arnount of material that

would have to go through extra processing since only the premix would need to be

treated instead of the entire sait batch. This thesis primarily focuses on using

encapsulation methods for the preparation of premixes.

2.3 Seleetion Of A Vehicle And FortiQing Compounds

The selection of the right food vehicle and micronutrient compounds is of utmost

importance to any successful fortification program. In selecting the food vehicle the

target population, their habits, customs and beliefs and most importantly their safety are

of primary concem.

Iron and iodine deficiency impacts the highest number of people in developing countries.

The population at greatest risk is living in poverty with inadequate access to nutritionally

complete foods. This should be kept in mind when identifj4ng the fortification

approaches suitable to overcome the nutritional deficiencies.

A suitabie food vehicle is the one that meets the following criteria:

1.

II.

III.

IV.

v.

VI.

I t is crntrally processed

It is technologically and economically fortifiable. The marginal extra cost if any

should be such that the fortified food rernains within economic reach of the

poorest groups who are likely to be most at risk or the cost m u t be borne by

health agencies/govemments.

It can be made available to the target or total population through an effective

distribution system.

It is consumed in fairly constant or predictable arnounts. Allowing calculation of

required fortification levels and ensuring no risk of over-consurnption.

It will not result in significant change in taste, texture. appearance or colour on

addition of forti ficant.

It is acceptable and frequently consumed by the target or total population.

Salt is one of the very few food commodities that meets nearly al1 of the criteria for a

food fortification vehicle. Salt has been successfully fortified with iodine since the early

1900s. Iodised salt has virtually eliminated IDD in most developed nations. Salt that is

double fortified with both iron and iodine is however a more recent idea. Many groups

have tried to double fortiQ salt with varied arnount of success. University of Toronto has

successfully dernonstrated that iodine dispersed within a dexvin matrix through spray

drying and ferrous fumarate added to salt resulted in a formulation that was stable for up

to one year (Diosady 1996, Diosady et d. 1998). India has also initiated several

pmgrams to double fortifi salt with iron and iodine and has s h o w that a combination of

chelating agents (Sodium hexametaphosphate, or EDTA) and other stabilising agents

such as sodium bicarbonate and sodium caseinate can improve the long terni stability of

fonified sait (Narasingha Rao 1994).

2.3.1 Choice And Dosage Of Iodine Compound

Iodine is normally introduced as the iodide or iodate of potassium, calcium or sodium.

Table 2.2 below shows some important physical properties of these compounds:

Table 2.2: Physical properties of iodine and its compounds

Source: CRC Handbook 1964

Salt iodization programs use both potassium iodide (KI) and potassium iodate (Kï03)

%

iodine

100

86.5

65.0

76.5

59.5

85.0

64.0

Mol.

wt.

253.8

293.9

498

166.0

214.0

149.9

197.9

Name

lodine

Calcium

iodide

Calcium

iodate

Potassium

iodide

Potassium

iodate

Sodium

iodide

Sodium

iodate

extensively for iodization. Table 2.3 lists typical iodine sources and iodization Ievels:

Chernical

formula

11

Cal2

Ca(IOt)2.6H20

KI

K I 0 3

NaI.2HI0

NaIO3

m.p '

OC

113

740

d. 35

686

560

651

d.

b.p

OC

184 atm

1100

--

1330

d.

1304

-

Solubility in water @IL)

O'C

--

646

-

1780

47.3

1590

-

2O'C

-

676

1 .O

1440

81.3

1790

25.0

3OC

0.3

690

4.2

1520

117

1900

90.0

4OoC 1 6O0C 0.4

708

6.1

1600

128

2050

150

0.6

740

13.6

1760

185

2570

210

Country

Austral ia -

-

7

- - - -

- -

- - - - -

Iodine compound used

Carneroon

Levei Of Iodization At

Potassium iodate

I

Production (mg Ikg Salt)

65

Potassium iodate

Canada 7

China 1 Potassium iodate

50

40

Ecuador

Potassium iodide

I

Potassium iodide 1 40

Germany

77

India

b

Indonesia

Nigeria 1 Potassium iodate 1 50

Potassium iodate 1

Kenya

35

Potassium iodate

Potassium iodate

30

25

Potassium iodate

I

Panama 1 Potassium iodate/iodide

100

67- 1 O0 I

USA 1 Potassium iodide

--

Table 2.3 Salt iodization levels in selected countries Source: Universal Salt Iodization resource Kit CD-ROM, Micronutrient Initiative.

The high solubility of EU enables dispersion by atomized sprays on very dry crystals.

However, KI in sait is not very stable and can be easily lost by oxidation to iodine under

the conditions mentioned in section 2.2. It can also be lost if the iodized salt packages

become damp, resulting in migration of iodide fiorn the salt to the fabric, and subsequent

evaporation if the fabric is pervious. This loss can be lessened when the salt is very pure

(+99.5%) and dry (moisture less than 0.1 %), and by the addition of stabilizers such as

sodium thiosulphate and caicium hydroxide, andor drying agents such as magnesium

carbonate or cafcium carbonate.

77

Zimbabwe

Most people in iodine deficient areas use unrefined salt that c m be effectively

supplemented with Ho3 without added carriers or stabilizers, as iodate is more stable

Potassium iodate 50

under adverse climatic conditions. It is also less likely to migrate from the bag as it is

only sparingly soluble in water at low temperatures. The Joint FAOIWHO Expert

Comrnittee on Food Additives has approved the Provisional Maximum Tolerable Daily

Intake (PMTDI) for iodine of I mg/day from al1 sources. Even at the highest dosages

currently used, iodine intake through iodized salt is unlikely to exceed 20% of this value.

In double fortification with ferrous compounds it would be prudent to use KI since

ferrous cornpounds c m easily reduce iodate to iodine and result in oxidation of iron from

ferrous to femc. The presence of dexuin, which is also a reducing agent, would also

accelerate this reaction.

The recommended minimum daily requirement of iodine varies from l5Oug to 200ug.

There is no universal specification for the level of iodine to be added to salt to achieve

this dose. This is because nurnerous factors influence the selection of an appropriate

level for a given population, including per capita consumption of sait in the region, the

degree of iodine deficiency in the region, transit losses, and the required shelf life. The

per-capita consumption of sdt in different countnes around the world varies fiom 3g to

2Og per day. (Venkatesh Mannar et al 1994)

23.2 Selection And Dosage Of Iron Compound

The Iron source or fortificant has to be bioavailable, safe, affordable, and relatively

stable. It also has to conform to food and dmg regulations like any other food product.

The bioavailability is dependent on the presence or absence of iron enhancers and

inhibitors present in the diet, the iron status of the individual, the amount of iron present

in the meal. the form of iron and other physico-chernical factors such as particle size and

surface area of the iron particle (Bjom-Rasmussen, 1976)

The selection of an iron source often entails a compromise between the use of inert

compounds that are poorly absorbed and chemically reactive forms with high

bioavailability. Highly soluble iron forrns have the highest bioavailability yet are also

most likely to affect the stability, coloiir, and odour of foods. Ferric iron sources on the

other hand are more inert and have lower activity but are poorly absorbed (Gillespie.

1 996).

The average daily salt consurnption is around 10g per person. Assuming that this will

supply one third of the 3mg daily iron requirement, through a fortificant with a

bioavailability of 1 O%, the target iron level in sait needs to be 1 mg/g or 1000ppm.

Excess iron is toxic, causing vomiting, diarrhoea, and damage to the intestine. Iron

consumed in excess arnounts over longer periods of time causes iron overload disease

(haemochromatosis). This condition is potentially fatal but treatable. The symptoms of

excess iron include skin pigmentation, results in liver disease, diabetes rnellitus,

hypothyroidism. chronic fatigue. arthritis. and may cause infertility and impotence. More

than 6Omg/kg body weight iron is toxic. A person weighing 60kg would therefore need

to consume 3.6 g of iron or 3.6 kg of salt fortified at IOOOppm Fe to be harmful. Normal

salt consumption is approximately 1 Og per day.

There are several iron compounds that could be used in salt fortification. Their choice

depends on their bioavailability, colour. solubility and stability over the long nin. The

table below lists the sources of iron and their relative cost and relative bioavailability:

Common Vehicles I KEY: G=Good. F=Fair. P=Pwr - = Information not availablc

R=Rccornmcndcd. V-Vakible. NR=Not rccommendcd

Rrlativc Cost Factor: = 100 X Bioavailability factor in humans

% iron

Bioûvailability factor G= 1. F=2. P-3

Freely water soluble Ferrous sulphate.7H20 Ferrous gluconate Ferrous lactate -- -

Ferri~ ammonium citrate Ferrous ammonium sulphate Ferric choline citrate Slowly soluble Dned ferrous sulphate Ferric glycerophosp hate Ferric citrate Ferric sulphate Ferric sacchante Ferric chloride Poorly soluble Ferrous fumante Ferrous succinate

Ferrous citrate Almost insoluble or insoluble Ferric pyrophosphate Ferric orthophos~hate . . Sodium uon ~ v r o ~ h o s ~ h a t e .- . . Reduced elemental iron

a. Reduced by hydrogen b. Reduced bv carbon monoxide

d

c. Carbonyl iron d. Reduced by electrolysis

-

Femc oxide Femc hydroxide Ferrous carbonate Iron Corn plex Compounds Sodium Femc EDTA

Table 2.4 Commercially available iron fortificants and their effectiveness and use characteristics Source: A nonymous, XII INA CG Meeting Combating Iron Deficiency Anenrio Thro tigh Food Fort@ation Technoiogy. International ~Vutritional Anemia Consultative Group, Washington, Decernber 1990, page 18, table 3.

Ferrous fumarate has proven to be one of the best compounds for iron supplementation

(Fomon et al. 1992) due to its stability and high bioavailability. The disadvantage is that

it is brownish red in colour and unsightly when cornbined with salt. Ferrous sulphate is

an effective and relatively inexpensive compound of choice but it is highly soluble in

water and is usually easily oxidized and has a pronounced unpleasant taste. When added

to salt ferrous sulphate is easily oxidized forming femc chloride by reacting with sodium

chloride. The formation of femc chloride is usually distinguished by the yellow colour

of the salt. Encapsulation of ferrous sulphate with partially or fully hydrogenated fats

increases its stability and at the sarne time its bioavailability is not compromised (Fomon

et al. 1992 - Hurrel. pg 42-43)

Figure 2.2 Salt fortified with ferrous sulphate heptahydrate after exposure to 100% humidity and

40°C over 3 mon ths, ferrous sulphate (lefi), encapsulated ferrous sulphate (righ t)

2.4 Developing A Method For Double Fortification

The benefits of adding iron and iodine simultaneously to salt are obvious and have been

discussed in the previous sections. Developing a technique that can be applied in doing

so successfully without compromising the appeamnce, stability, taste and texture of the

sait and keeping the whole process within suingent cost criteria is a far greater challenge.

University of Toronto and in particular the food engineering group under the supervision

of Professor Diosady has made significant strides towards developing stable double

fortified salt. The approach has been based on the idea of keeping iron and iodine from

contact with impurities, moisture and other reactive agents in salt. A simple technique of

doing so in food engineering is to create a waterproof barrier around the active

ingredients. This procedure is known as encapsulation or microencapsulation.

Encapsulation of substances to preserve their characteristics or to enhance their

performance and palatability is not a new idea Many different products from

pharmaceuticals to foods flavon increasingly make use of microencapsulation

technologies. Its use in salt fortification however has not been exploited due to the high

costs of typicai encapsulation processes.

The idea of physically separating the active ingredients from hannful effects was tint

studied using spray drying rnethods. This breakthrough involved dispersing Ki within a

particle made from dextrin, a partially water-soluble starch compound, which sewed as a

physical barrier between the two elements (iron and iodine). The double-fortification

technology was developed with support from the Micronutrient Initiative (MI) and IDRC.

MI is a non-profit organization that aims to eliminate health problems resulting fiom

deficiencies in iron, iodine, vitamin A and other essential micronutrients.

This spray drying system gave good results both in t ems of stability of the double

fortified salt and its acceptance in field studies performed in Ghana which involved 5000

people (Diosady 1998, I&II).

With the success of spray drying, a method which was less expensive, was desired. This

report discusses the techniques which can be applied as an alternative to spray drying and

how some of the disadvantages of spray drying were overcome.

There are several aspects which nred to be considered in fortiQing salt using

microencapsulated ingredients:

1,

II.

III.

IV.

The iron and iodine premix must have the same particle size as that of salt to

prevent segregation.

Iodine dosage requirements are low, and in order to avoid risks of overdose, it

needs to be diluted before encapsulation to main a safe level for addition to salt.

The particles have to be unifom before encapsulation can take place.

The particles have to have suficient hardness and tensile strength to avoid

breakdown during mixing with salt.

V. When mixed with sait the distribution of the particles should be uniforni,

segregation of premix within the sait can lead to overdose or lack of micronutrient

in the diet.

In principle, design of the particle was simple, have the active nutrient in the centre

distributed within and edible rnatrix, encapsulate the particle with a water impervious

layer. The particles should be about 100-200 times more concentrated than the required

dose. These would then be diluted with normal salt to attain the required iodine and iron

levels within the salt. As it is unlikely that each processor cari actually make the

encapsulated micronutrients, a premix must be centnlly made and distributed to

processors, to mix with local salt. Practical considerations limit the amount of premix to

- 1% of the salt (Diosady, 1998). Higher dilution ratios would lower costs but at the

sarne time increase risks of overdose.

In designing premix containing the micronutrients for addition into salt, several criteria

had to be considered. The daily requirernent of iodine is very low and therefore the

concentration of iodine in the premix should not exceed 5%. Iodide or iodate salts could

thus not be directly encapsulated, as they could be potentially toxic at those leveis. Iron

compounds on the other hand could be directly encapsulated. as the daily requirement for

iron is higher. The particle size of the premix and the salt also had to be similar to

prevent segregation of micronutrients which would result in delivery of very high or low

doses of nutrients to the consumer.

Fortilled Particle

Encapsulant

Active ingredient Core ! \

' Inert matrix (fillers and binders)

Figure 2.3 Cross sectional view of an ideal encapsulated particle

Spray drying proved to be an effective method for addition of active nutrients to the salt.

Unfortunately spray drying is expensive and produces very fine particles which easily

segregate unless the salt is milled to match the particle size. Milling salt would be

tremendously costly and would also alter the flow characteristics of the salt which would

not be readily accepted by consumes. A method that would produce particles with the

particle size typical of local salt, containing the required dosage levei, and physical

characteristics was thus needed. The cost and complexity of the enrire process also had

to be within the reach of developing countries.

2.4.1 Size Enlargemen t

Size enlargement is any process whereby small particles are gathered into larger,

relatively permanent masses in which the original particles can still be distinguished. The

terrn encompasses a variety of unit-operations or

particle agglomeration. Agglomeration processes

processing techniques dedicated to

can be loosely broken down into

agitation and compression methods. Agitative processes include fluid-bed. spray-drying,

pan (or disc), drum, and mixer grmulators. Compression agglomeration processes

include tableting or briquetting, and extrusion processes.

The leed in size enlargement processes typically consists of a mixture of solid

ingredients, referred to as the formulation, which includes an active ingredient, binders,

fillers or diluents, lubncants, andor colours or dyes.

The agglomeration c m be perfomed in several ways. The solvent or slurry can be

ûtomized onto the bed of particles which either coats the particle or granule surfaces

promoting agglorneration, or the spray drops c m form small nuclei in the case of powder

feed which subsequently c m agglomerate. The solvent or slurry may contain a binder, or

solid binder may be present as a component of the feed. Altematively, the solvent may

induce dissolution and recrystallization of soluble particles of solid binder.

At the level of manufacturing plant, the size-enlargement process cm involve several

peripheral unit operations such as milling, blending, drying and or cooling, and

classification to increase product yield and uniforrnity. In addition an added

encapsulation step may be involved to M e r enhance product characteristics.

2.3.2 Approaching The Design Of Size Enlargement Processes

2.4.2.1 Agglomeration Kinetics

Four key rate processes control granulation. These include wetting, coalescence or

growth, consolidation. and breakage. These processes combined control granule size and

porosity, and they may be influenced by formulation or pmcess design changes.

Growth

I I f(size, porosity)

l 1 f(openring variables + materid vririablcs)

L

tnsolidation

Figure 2.4 The rate processes of agitative agglomeration, which incfude powder wetting, granule growth, granule consolidation and granule attrition. Source: Perry9s Chernical Engineer's Handbook, 71b Ed. 1997. pg 20-59, Fig 20-63.

Initial wetting of the particles by the binding fluid is strongly idluenced by spray or fluid

distribution as well as feed formulation properties. In the coalescence stage, partially

wetted primary particles and larger nuclei coalesce to form granules composed of several

particles. The term nucleation is typically applied to the initial coalescence of primary

particles in the imrnediate vicinity of the larger wetting drop. As the granules grow, the

compaction forces of the bed, due to agitation, consolidate them.

2.3.2.2 Product Characterization

Powders are agglomerated to change their physical and physicochemical properties. Key

agglomerate properties are size, porosity. bulk density, strength, and their associatrd

distributions. These properties directly affect end-use attributes of the product such as

attrition resistance. flowability, bulk-solid perrneability, wettability and dispersibility,

appearance, or active-agent reiease rate.

Size: Aggiomerate mean size and size distribution are both important properties.

Sieve analysis is the most common sizing technique. Handling of the sarnple durinç

sieving analysis can cause changes to the size distribution through coalescence or

breakage. Online measurement techniques using laser diffraction techniques are now also

available.

Porosity and Density: There are three important mesures of density of granular

or agglomerated materials:

Bulk density pb (related to the volume occupied by the bulk solid), the apparent or

agglomerate density pg (related by the volume occupied by the agglomerate including

interna1 porosity) and the true or skeletal-solids density p,. These densities are related to

each other and the interagglornerate voidage ~ b , and the intra-agglomerate porosity E,:

Strength of Aggiomerates: Agglomerate hardness c m be quantified through its

tensile strength, its resistancc to attrition (fi-iability), the rate at which it can disintegrate

in a Iiquid medium, or its fracture toughness. The strength of agglomerates is important

if the agglomerates are subjected to further processes such as encapsulation. sieving, or

mixing with another solid.

2.43 Size Enlargement Equipment And Practice

Size enlargement equipmrnt can be divided into 3 major categorîes. tumbling

granulaton; spray granulators, fluidized bed gnnulators. and pressure compaction

granulators.

3.4.3.1 Tumbling Grmulators

In himbling granulators, the particles are set in motion by the tumbling action caused by

gravitational and centrifuga1 forces. The particles are thus caused to collide with each

other and consolidate into larger particles. Tumbling granulaton are nonnally used ir.

making particles in the size range of lmm to 20mm. Drum and disc (pan) granulators are

the most common types of tumbling granulators.

Disc or pan granulators consist of a rotating, tilted disc or pan with a rim. The powder is

fed onto the pan and the binding solution or wetting agent is sprayed as the disc forces

the powder to tumble within the pan. It is important to balance the pan angle and rotation

speed in order to ensure that the powder does not flow as a dead mass or is Forced to the

rim of the pan due to centrihgal forces.

The required disc rotation speed is given in terms of critical speed, Le.. the speed at

which a single particle is held stationary on the rim of the disc due to centripetal forces.

The cntical speed. N, is given by:

Where g = acceleration due to gravity

@ = angle of the disc to the horizontal

D = Diameter of the pan

Disc granulaton range in size from laboratory rnodels 30 cm in diameter to production

units of 10 meters in diameter with throughputs of 100 tonh .

Wan et al. ( 1985 & 1986) suggests that there are many factors that can affect the particle

characteristics in a pan agglomerator such as size. hardness. friability, and bulk density.

The important factors among these are:

Pan loading: Increasing the mass of material increases the average pellet

diameter and also increases the bulk density and friability of the particles.

Residence tirne: Increasing the residence time of feed increases the average pellet

diameter but after some period the added agitation has a negative effect on particle size

due to breakage of agglornerates by attrition forces. Increased residence time however

increased the sphericity of pellets.

Agitation speed: Increasing the agitation speed decreased the average pellet

diameter. At very high agitation speeds the bulk powder is immobilized on the pan rim

due to centrifuga1 forces. Very low agitation speeds are also not efficient since

insufficient momenturn is created to cause the rolling of the powder.

Inclination angle: The angle of inclination does not have much effect on the

pellet characteristics. It does nevertheless have a significant effect on the efficiency of

the process in terms of spillage, spray-powder contact and the overall rolling motion of

the bulk powder.

Powder formulation: This is probably the most important variable in

Pelletization technologies. The choice of binder, bulk material, filler and solvent are of

utmost importance to the characteristics of the final pellet.

Mixer granulators work on a similar principle as pan granulaton, the only difference

being the powder motion is through paddles or mixing blades as opposed to centrifuga1

and gravitational forces.

2.4.3.2 Fluidized Bed and Related Granulators

In fluidized bed granulators, the particles are suspended in the chamber by air nther than

mechanical agitation. Fluidized bed technoiogy is one of the rnost versatile techniques

for both agglomeration and coating/encapsulation applications. The product also has a

narrow particle size distribution. The simplest fluidized bed granulator is the Wurster

colurnn show in figure 2.5, many versions of this design are now in use the only

difierence between hem being the orientation of the colurnn, air handling unit, and the

spray nonles. Fluidized bed columns essentially operate on a batch mode although some

continuous cofumns are available.

Figure 2.5 Cut-out view of i~ Wurster Process Cham ber

..L ciopred fiorn Vunclcguer. 1 9 74, pg 146

2.4.3.; Extrusion Granulators

Solid spherical pellets c m also be produced using extrusion technology. The process

involves extrusion of wened material into cylindrical segments. breaking the segments

and then rolling them into solid spheres. This is also known as spheronization. In

addition to obtaining a cylindrical product, there is aiso some degree of compaction that

occurs during the rolling process.

The final sphere size in determined by the size of the extruded cylindea, as a general rule

the final product diameter is approximately equal to the diameter of the perforations on

the extruder die. The advantages of using this process are the product size is very

uniform, the process time is very shon, and pellets with active ingredient content of as

high as 90% have been produced (Conine and Hadley, 1970).

To prepare the solid spheres, the following operations are involved: (1 ) dry blending, (2)

wet granulation, (3) extrusion, (4) rolling in a marumerizer, (5) drying, and (6) screening.

The mammerizer consists of a shallow cylindrical chamber with a horizontally spinning

plate. The extmded cylinders are rolled against the manimerizer walls by the spinning

plate into spherical balls.

2.3.3.4 Spray Drying

Spray drying is widely used in the flavour industry to protect volatile and reactivr

matenals from degradation. Although most oflen considered a dehydration process.

spray drying can be used as an encapsulation process when it entraps "active" matenal

within a protective matrix.

The process is conducted in a spray dryer such as the one s h o w in figure 2.6 below. The

matenal to be dried is sprayed in the form of small droplets into a cylindrical chamber. in

which hot gas circulates, supplying the heat necessary for evaporation. Atomizers are

chosen according to the material nature. The powder produced is collected at the bonom

or at one of the sides of the drying chamber

Figure 2.6 Spray Dryer

Source: http://www.enrropie. fr/En/dryer/ index-htm

2.5 Encapsulation

Once a uniforrn core pellet is achieved, fominç a physical barrier around it can funher

protect the active ingredient within the core matrix. This procedure is called

encapsulation or microencapsulation. There are several factors involved in achieving a

proper film around a particle and these include: (1) the choice of encapsulant, (2) the type

of solvent used, (3) The encapsulation procedure, and (4) the thickness of the film itself.

Encapsulation if done properly generally protects the active ingredient. There are many

different encapsulants which are used in the food and dmg industry and also in many

chemicai industries such as fertilizers for controlled release of active ingredient and for

increasing the shelf life, palatability and appearance of food and drugs.

In double fortification of salt, the main concem is to preserve the stability of iodine and

iron and thus it would be beneficial to keep the active nutrients. Le. iron and iodine from

corning into contact with water and other impurities in the salt. Thrre is however a

compromise which needs to be reached when encapsulating iron and iodine, more

protection could increase the stability of iron and iodine but at the sarne tirne it may

greatly reduce the nutrients bioavailability. It is therefore important that the problem be

approached fiom both sides.

2.5.1 Choice Of Encapsulant

Encapsulation c m be generally classified into three distinct groups: sugar coating, film

coating, and compression coating. Sugar coating is probably the one most commonly

used, perhaps for historical reasons. Film coating however is quickly replacing sugar

coating in man. application due to the wide range of encapsulants that are now available

and its relative ease of use. low process times, and greater overall efficiency.

The choice of encapsulant is of paramount importance to any encapsulation process. The

properties of the final product c m be greatly altered by the encapsulant and its properties.

There are several encapsulants which were investigated in this study and are commonly

used in the pharmaceutical and food indutries, these are listed in the table below.

l I 1 organic solvents I

Encapsulant

1 10- 15%. sol. in aq.

Common solvents Soiubiity in water

Shellac

I 1 solutions of

iMelting point

Soy stearine 1 Insoluble Ethanol. methylene ( 65°C

I I 1 methylene chloride.

1 1 5- 1 20°C t

Zein Insoluble

Insoluble 95% Ethanol. ether

ethano lamines.

Aq. alcohols,

l

d. 300°C

1 aq. solutions with

Polymethyl 1 Insoluble

methacry late

Polyethylene glycol

pH> 1 1.5

Methy lene chloride.

E thy lcellulose

Depends on extent

Soluble

Palmitic acid

1 ceilulose 1 on amount of 1 chloride

insoluble

Carboxy methyl

absolute alcohol

Water. methylene

Insoluble

Table 2.5 Pro perties of selected enca psuiating agents

Previous studies have shown that eliminating rnoisnire is of utmost importance in

stabilizing iodised or iodated salt. It was therefore desirable to have an encapsulant

which would was impervious to water. Also the salt can get very wet under humid

conditions and the encapsulant should not deteriorate under these conditions.

of polymerization

30-50°C -

chIoride

Methy lene chloride.

Solubility depends

I 1 substitution

depending on MW

Sofiens i 40°C

ethyl acetate.

methano l

Hexane. methy Iene

chloride, hot alcohol

Water, methylene

I

63 -6JUC

The important criteria for a suitable encapsulants are; it should be edible, it should be

easiiy digested by the body, it should conform to local beliefs, it should meet food

regulations, and it should not impart a highly distinguishable colour or taste to the sait.

2.5.2 Surface Characteristics Of Films

For optimum results, the film surface should adhere to the solid underlying surface and

form a continuous unbroken shell around the particle. Although this is a goal of all

encapsulation processes. it is almost impossible to achieve. Any film will have

imperfections but these usually cm be reduced to acceptable levels with the right process

conditions and proper selection of encapsulant.

Porter (Tablet Coating. 1-IV) classifies film imperfections into the following types:

Picking: occurs when drying is inefficient, or where an over-ambitious rate of

application of coating solutions is utilized. Al1 of these produce a wet bed. this results in

adjacent particles sticking together and on subsequent turnbling, are broken apart. This

leads to films fragments king removed from one particle and sticking to another.

Peeüng: is an extension of picking, this is when the encapsulation bed is ailowed

to become very wet resulting in attrition and wearing off of larger sections of film onto

the bed.

Bridging: Occurs when the film surface foms a bndge across and indent of

fracture on the particle surface. The film section over the indent is thus not bonded

properly to the underlying surface and is easily chipped off dunng agitation or tumbling.

Orange peel effect (roughness): This usually occurs when a spray technique is

used to transfer the film ont0 the particle. Tiny droplets of solution are continually dned

on the surface and are unable to coalesce resulting in a rough film surface. This can be

reduced by using a higher spray rate, increasing the drying time, or using a plasticizer.

Cracking: occun when there are stresses on the particles and the film surface is

not elastic enough to absorb the stresses. This can be reduced by addition of plasticizers

or using a more elastic film.

2.5.3 Solvent Selection

The solvent used to dissolve the encapsulant will also influence the final film properties.

The volatility of the solvent will determine the process conditions and the drying rate.

Long drying times will result in a wet encapsulation bed and lead to picking, peeling and

secondary agglomeration of particles. A very fast drying rate wiil result in rough film

surfaces, and cracking of the film.

The flammability, toxicity and overall hazard limits of solvents also have ro be kept in

mind and handlcd accordingly. Two solvents, 95% erhanoi (food grade) and methylene

chlonde were used to dissolve the encapsulants before spraying.

Methylene chloride is widely used in the pharmaceutical industry for various enteric

coating and film coating processes. It is not flarnmable but being a chlorinated

hydrocarbon, it needs to be handled with care. There are some concems with using

methylene chlonde as it may be a possible carcinogen. Since only small batches were

encapsulated in the labontory the exposure to methylene chlonde was minimal. Also al1

encapsulation and agglomeration was performed in the fumehood to avoid exposure to

solvents. At an industrial level, spraying a melted encapsulant as opposed to its solution

is more feasible.

3. EXPERIMENTAL

3.1 Materials

The chemicals that were used in this study are listed in table 3.1 below with their

specifications and suppliers.

Chemical Supplier Carboxy methyl cellulose Herman Laue Spice Co. Carrageenan Herman Laue Spice Co. Dextrine Casco Ethanol Aldrich Ferrous fiimarate Aldrich Ferrous sulphate heptahydrate Aldrich Guar Gwn Herman Laue Spice Co. Hydroxy propyl cellulose Herman Laue Spice Co. Methyl methacrylate Sigma Methy lene chloride BDH chernicals Microcrystalline cellulose Herman Laue Spice Co. Palrnitic acid AIdrich Polyethylene glycol (PEG ZOO0 Sigma

Description Food grade Food grade Modified starch # 7071 Food grade ACS grade ACS grade Food grade

Analyticai grade - 1 1 & PEG 8000) 1 1 1

1 1 - Soy stearine 1 Canamera foods 1 Fully hydrogenated soy oil

Potassium iodate Potassium iodide Shellac Sodium chloride (salt) Sodium hexametaphosphate

Table 3.1 List of chemicals used

Aldrich Aldrich

Cargill foods Inc. Aldrich

Zein

3.2 Equipment

ACS grade ACS grade

Topflo' uniodised salt ACS grade

Pan agglomeration was c h e d out in a rotating pan. The pan was 30 cm in diameter and

Sigma

6 cm deep. The pan inclination angle and the rotation speed were variable. A diagram of

(MP - 60°C) Food Grade

the pan is shown in figure 3.1.

SlDE VlEW FRONT VIEW

Figure 3.1 Diagram of rotating pan used for agglomeration and spray coating of particles.

The same pan agglomerator was used for spray coating the agglomented particles. A thin

layer chromatography (TLC) spray bottle (250ml) from VWR tvas used as an atomizer

for spnying the binder solution and encapsulant solution during agglomeration and

encapsulation runs respectively.

Pilot scale spray drying was performed at the Guelph Food Technology Centre with a

Bowen BLSA spray dryer.

Co-crystallization was performed in g las beakers of different sizes and stimng was

either done through a BrinkmannB stirrer or a stimng rod attached to a rnotor. A water

bath was used to aid in evaporation of the N a C M Iiquor.

Dry blending of solid powders was done in a glas jar for small batches, and in a LeRoy

Somer 5L i-ibbon blender for larger batches. Occasionally. when it was necessary to mil1

the agglornerates to smaller sizes, a Braun cof3ee gnnder and a Retsch mill, mode1 No.

ZM1 were used as appropriate.

UVNis spectroscopy was done in a Perkin Elmer UVNis spectrophotometer.

3.3 Experimental Procedure

3.3.1 Pan Agglomeration

A typical pan agglornention run consisted of blending the dry powder formulation in the

ribbon blender or g las jar. The powder was thrn fed in to the pan and the pan angle and

rotation speed were adjusted until a cascading motion in the pan was achieved. The

binding solution (either water, or other dissolved binding agent in water) was then

spnyed ont0 the powder in the pan using a TLC atomizer hooked up to an air supply at 3-

jpsi. Once the powder was agglomerated, the granules were placed in a baking pan and

dned in an oven at 50°C until the particles were dry to touch. The aggregates were then

separated by size using a stack of Tyler@ sieves and a Ro-tap@ sieve shaker for 7

minutes.

3.3.2 Spray Coating

Spray coating of the particles was also done in the pan agglornerator. nie particles to be

encapsulated were fed into the rotating pan and set in motion. The encapsulant was

dissolved in either alcohol or methylene chlonde and sprayed using a TLC atomizer ont0

the particles. It was sornetimes necessary to dry the particles in-between spraying. This

was done by using a heat gun. The m a s of the particles was measured before and afier

each run to determine the level of encapsulation. The concentration of the encapsulant

was varied to alter its viscosity to enable spraying.

33.3 Spray Drying

Semi pilot scale spray drying r u s were performed at the Guelph Food Technology

Centre (GFTC). The centre's Bowen BLSA spray dryer was used for both runs. The two

nins were canied out on blarch 25, 1999 and March 26, 1999. The feed solution

contained 12% (wlw) solids. The dextrin was first dispersed in a 1 : 1 mixture with water

in a blender. The slurry was then diluted with enough water in the feed tank to rnake a

12% solids feed mixture. KI equal to 2% of the total solids was added to the feed tank

directly. The feed solution was preheated to 88OC with mixing before being pumped

through the spray dryer. The following spray dryer conditions were used for both mns:

Variable Set point

Nozzle size

L I

Inlet heater temperature measured 1 157+2'C

80 (medium)

lnlet heater temperature set point 162 - + 2°C

I 1 inlet temperature 1% 2 1°C

Outlet temperature 84 + IUC

Cyclone Pressure drop 1.49 kPa

Temperature at the bonom of the chamber

I

Feed Temperature 1 88 + 4°C

87 5 2'C

Air pressure at dual nozzie

- - - - - - -- - - -

Table 3.2 Operating conditions for pilot scale spray drying runs.

275 kPa

Moyno purnp setting

33.4 Co-crystalliza tion

We attempted to produce crystals of sait containing up to 5% of KI or KI03 to produce

the appropriate dilution of KVKI03, and to obtain particles which would not segregate on

mixing with salt. The flow diagram of a typical approach which was used is as follows:

I

3

,/ /'

/'

: Paddle mixer j ,, O , 95 g NaCl ,,y' : 4 (Evaporation) i-;Lb

/' ,' t a I 60°C 1

/ / I

I /

DRY 1

I .' IODINE CONTENT ')

y ANALYSIS L - -P. - - -- A

5gure 3.2: Flow diagram of a typicai CO-crystallization run

3.4 Analytical Methods

3.4.1 Moisture Content

The moisture content of samples was determined gravimetrically. Samples weighing noi

less than 5g were weighed into alurninum bats previously dried in the oven at 1 lOoC to

remove moisture. The samples were then dned in an oven at 1 1 O°C for 12-24 hours or

until two identical weight readings were achieved. The difference in weight was the loss

in moisture of the samples and the % moisture determined as foIlows:

% Moisture = Mass of dry sarnple * 1001 Mass of original sample

3.4.2 Iodine Analysis

3.4.2.1 Iodate Analysis

The iodine content of iodated samples was measured through iodometric titration. This

method involves using a reducing agent to liberate free iodine. Excess KI is then added

to stabilize the fiee iodine. The presence of free iodine is indicated by the addition of a

few drops of 3% starch solution. The free iodine is then consumed by standard sodium

thiosulphate solution. The iodine content cm easily be calculated from the volume of

thiosulphate needed to consume the fiee iodine in any given sarnple.

3 .-LX Iodide Analysis

The iodine content of iodized samples was measured using epithermal neutron activation

analysis (ENAA) using a slowpoke nuclear reactor with the help of Professor Ronald

Hancock at the Royal Military College in London, Ontario.

In this method, 1-2 g samples of salt are weighed into polyethylene vials. These vials are

then shielded with a cadmium shell and imdiated at 10 kW for 3 minutes using a neutron

flux of 5.0 x 10" cm-*s". The cadmium shell is used to reduce interferences due to the

high proportion of chlorine and sodium present in the sarnple. Following irradiation,

there is a time delay of 6 minutes, after which the gamma emissions at 443 keV are

measured using a hyper pure germanium based gamma ray spectrometer. The

concentrations OF iodine in the samples can then be calculated based on a calibration

curve obtained from a series of standard samples ranging in iodine concentration From

200 to 2000 ppm.

3.33 Iron AnaIysis

Iron analysis was performed using the method developed by Harvey, Smart and Edwards

(1955). This meihod involves forming a complex of iron(1I) and iron(11l) with 1 JO-

phenanthroline. The absorbance of the resulting complex is then rneasured at 396 nm and

520 nm and correlated to calibrated data to determine the total iron and the ferrous

content of samples sirnultaneously. The main advantage of this method is that it not only

gives the total iron content but also differentiates between ferrous and femc iron.

3.4.4 Particle Size Distribution

Particle size distribution analysis was performed using a set of Tyler@ screens ranging in

size from 50pm-4mm and a RoTap@ sieve shaker. Sarnples, no less than 25 g were

separated using the stack of sieves and a RoTap sieve shaker for 7 minutes. The

separated particles were then weighed to determine the fraction of particles of the size

range of two adjacent sieves.

ÿÿ p.^;-::-.;.;:--- .. .$-. .Y- .-: .: . t-

Figure 3.3 A Ro-Tap sieve shaker with a stack of sieves

3.5 Sample Storage And Packaging

AI1 sarnples which were tested for long term stability were placed in LDPE bags and

stored in a closed air tight oven maintained at 40°C and completely saturated with

moisture ( 1 00% RH). The samples were taken out of the oven at regular intervals and

analyzed for iodine and iron content and visually inspected for colour changes.

4. RESULTS AND DISCUSSION

The work presented in this thesis covers two major areas. Identification of a suitable

technique for double fortification of salt involved the physical aspects of producing

iodine and iron fortified particles to be added to salt. The methods uied here were CO-

crystallization and agglomeration followed by encapsulation.

The second area of study involved deriving a suitable formulation of the active

ingredients and the premix particles. In this part of the study the type of binders. fillers,

active inçredients, and several types of encapsulants were tested in terms of their

stability, colour, and taste.

The approach to double fortification of salt in this study was based on adding a premix

containing high concentrations of iodine and iron to regular salt. This approach was

different fiom the normal approach to fortiQing an entire batch of sa11 with iodine and

iron. This method has many advantages over traditional salt fortification programs.

Table 4.1 gives a cornparison of traditional fortification programs to the premix

approach:

Traditional Fortification Programs The entire amount of salt produced has to

1 ofthe salt 1 Consumen may not even notice the foreign

Premix Method Only the prernix has to be produced

be treated Encapsulation is not a feasible method as it would alter the texture, taste andhr colour

Only the premix, which norrnally does not exceed 1% of' the salt, is different.

/ Hard to implement at al1 levels of sait particles. Premix c m be made at central locations

production

Active ingredients may be sensitive to impurities present in the salt and formulation may need to be adjusted to

and easily distributed to many salt producers and added directly to the salt. Premix would be insensitive to the type of salt at the active ingredients are physically separated from other compounds resent.

salts of different kinds and compositions. Cost intensive, may involve extra

Table 4.1 Comparison of Traditional Fortification Vs. The Premix Approach

With the realisation that the premix method was more efficient. a suitable method for

producing premix particles with iodine content of about 3% was essential. The particles

had to have a uniform size, iodine content, and would need to look similar to salt for

consumer acceptance. It is essential to maintain the iodine content of the premix to less

than 5% since higher concentrations, although less costly, would require very big dilution

ratios and would increase the risk of overdose if any segregation were to occur or if the

mixing was not perfect. The same particle size distribution would ensure that the degree

of segregation would be minimised.

Added cost is minimal, only requiring purification and packaging changes, and also changes to the production line.

[ngredient may be s~raved on in solution

Co-crystdlization was the fmt method that was investigated for growing particles. The

idea was to precipitate NaCl onto seed crystals of KI03. The NaCl as a result would

blending of premix and salt. Cost would also be distributed by a factor equivalent to the dilution ratio of premix to salt. Premix must be dry mixed

encapsulate the KI03 crystal and protect it from reaction. Co-crystallization has been

appiied in some specialized products successfully.

Sixteen runs were performed here in trying to CO-crystallize KI03 and NaCl

simultaneously. The process panmeters that were varird were temperature of solution,

rate of evaporation and addition of precipitation aids.

A typical CO-crystallization run involved starting with a saturated liquor containing 95%

NaCl and 5% KI03. nie saturated solution was then slowly heated under gentle mixing

to evaporate the water and initiate precipitation of the crystals. Once most of the solution

had evaparated the crystals were filtered under vacuum and dried. The iodine content

was then determined by taking several samples randomly from the batch. On radier runs

it was round that the crystals lumped together upon drying and these lumps caked on to

the equipment. The amount of caking was greatly reduced in Iater runs by washing the

crystals with ethanol before drying. This removed any residual water.

It was found that most nins performed by CO-crystallization were unsuccesshil. The

particles obtained using this method were uneven in size. On some occasions the entire

batch caked and formed one large lump that had to be crushed d o m to size. The iodine

distribution was very poor within the batches and aiso between batches indicating that the

particle chemicai composition was highly non-homogeneous and could not be controlled.

Table 4.2 gives a s u m a r y of the results of the iodine content and the variation depicted

by the relative standard deviation (%MD) of batches produced by CO-crystallization.

1 3.3 55.0 Poor White Particles show uneven 2 8.3 114.0 Poor White surface c haracteristics 3 0.0 - Poor White - from white powder ta 4 2.6 10.0 Poor White translucent crystals. 5 5.7 9.5 Poor White

'

suggesting segregation 6 4.4 9.6 Poor White of NaCl and KI03. 7 5.7 4.7 Poor White 8 13.9 147.0 Poor - White 9 10.1 87.8 Poor White 10 6.3 12.7 Poor White 11 1.8 14.3 Poor White 12 1 . 0 ' 132.8 Poor White 13 2.0 24.8 Poor White 14 4.2 47.7 Poor White 15 3.8 16.5 Poor White 16 6.7 8 Poor White Mean 4.99 ,*CC= Co-crystallization Median 4.3

Mode l;:9 Standard Deviation 3.59 Sample Variance Range 13.9 Minimum O Maximum 13.9

, Confidence LeveI 1.57 I

(90.0%) I

TabIe 4.2 Summary of results of CO-crystallintion batches

I t is important to note that the variation in iodine content was due to the uneven

distribution of iodine and not due to analytical variation. This was confirmed by doing

replicate anaiytical determinations of iodine content on each simple. It was also found

that the variation between replicates of the same sample was less than 5%. This is s h o w

in table 4.3 below. The iodine content was measured by titrimetric methods, which is

highly reproducible and accurate.

Sarnple l~a t ch # Date Method i Iodine content (%KI03) Avg. SD %RSD, t 1

l Replicate i 1 3 3 4

1 1 5-14-98 CC 1 1.7 3.5 3.3 5.8 3 1.8 54.5 2 J.7 3.3 2.4 6 3 1.9 56.2 Average 11.7 3.4 2.4 5.9 3 1.8 55.3 SD 0.00 0.14 0.07 O. 14 %RSD 0.0 4.2 3.0 '2.4

3 - 64-98 CC 1 33.1 5.4 1.8 3.8 8 9 112.8 3 22.7 3.3 1.7 3.8 8 1 O l l ~ . - i ' Average 122.4 5.1 1.8 3.8 8 910 114.1 SD ,O.Q 0.07 0.07 0.00 % M D / 1.9 1.3 -1.0 0.0

Table 1.3 Variation in iodine content betweens samples and between replicate analyses runs.

The hieh variation in iodine content is probably dur to independent precipitation of K I 0 3

and NaCI. It is possible that the two species crystallized sepantely. This is likely since

crystallization is essentially a purification technique and crystal growth is more likely to

occur on like species. On closer examination of the crystals it was observed that rhere

was slieht bondinç brtween the KI03 and NaCl crystals. NaCl crystals are cubic and

MO3 crystals are monoclinic or cylindricd. The bonding between the NaCl and KIOl

was very weak however and the crystals broke apart easily. This was possibly due to the

shape of the crystals and the hgility of Ki03 crystals, which stuck out like needles from

the NaCl crystais. Since the K I 0 3 crystals were very fragile they broke off fiom the

NaCl crystals through attrition. A possible mechanism of this is suggested in figure 4.1

below.

La Cubic a crystal

Figure 4.1 Oiagram iIlustrating bonding and attrition o f K1O3 and NsCl crystals

From these results it was evident that another method had to be used to produce the

premix. Co-crystallization wasn't successfûl but we did discover that if we could form a

cake or larger aggregate witb even distribution of iodine within the cake. we could mil1

the larger aggregate to essentially any size and get particles with even iodine content and

size. With this in mind, a series of expenments with different formulations were

designed to try and agglomerate powder into larger aggregates. These are discussed in

the following section.

4.2 Agglorneration And Size Enlargement

Fine particles c m be agglomerated into larger granules easily using a range of processes.

This idea is applied in pharmaceutical and fertilizer industries extensively in growing

particles. While crystallization is more of a chernical reaction; size enlargement is a

physical process. At first we started with simply forming a cake by mixing fine

granulated salt (60%). KI03 (5%), NaHC03 (Wb), and dextnn (30Y0). The powdered

ingredients were wetted with water and thoroughly mixed to get an even composition.

The wrt paste was then dned to form a cake. The cake was found to have sufficient

hardness. and was milled using a cofTee grinder and a Retsch mill. The particles were

then separated to size using a stack of sieves. The agglomerates using this mediod were

found to be homogenous in terms of size. colour and iodine content. The iodine content

could also be controlled easily by altenng the powder formulation. Other binding agents

such as guar çum. cmgeenan and ethylcellulose were also tned as replacements for

starch but it was found that starch had better bonding strength.

22 Caking 4.3

distribution

Mode Standard Deviation Sample Variance Range Minimum

4

5.7 Narrow Pale yellow

4.3 0.27

0.07 0.6 4.1

Pale yellow Pale yellow

Narrow White Narrow White

Comments

Particles appeared homogenous, hard, and particle size could be controlled by milling and subsequent screening.

Table 4.4 Surnrnary of results of caking runs

Initial batches tumed pale yellow and it was suspected that this might be due to either

formation of iodine or due to Maillard reactions in the dextrin. Detemination of iodine

content of browned batches showed no change in iodine concentration and therefore the

browning was assumed to be due to Maillard reactions. Maillard reactions usually cause

browning of sugars under high temperatures and in the presence of moisture. The drying

temperature was reduced to jO°C from 100°C and subsequent batches did not show much

colour change.

In order to reduce the complexity of the premix and the process even M e r , a simpler

formulation was desired. From spray-drying experience (Diosady et al., 1998), it had

been proven that KI dispersed within a dextrin matrix was stable. The same formulation,

98% dextrin and 2% KI or KlO3, was thus used in agglomeration mns too. The dextrin

provided the bonding force as well as acted as a diluent/filler.

Caking provided a steady supply of premix core particles but it also involved cnishing the

larger agglomerates. The crushing step was found to be energy uneconomical and

redundant and therefore a method of agglomeration where the particle growth rate could

be controlled was desired. If the growth rate is controlled and particles are not

agglomented beyond the required size, crushing could be reduced or eliminated. We

therefore looked into different s i x enlargement processes and selected pan

agglomention as an alternative method. A lab scale pan agglomentor, shown in figure

3.1. was built with a 3Ocm x 6cm pan anached to a variable speed moior. Pan

agglornerators are used extensively to form pellets. The sizes of the pellets in a pan

agglornerator depend on spray droplet size. powder formulation, pan rotation speed. and

angle. Pan agglornerators can also be used in a continuous mode.

It was found that pan agglomeration could be used very easily to fonn premix granules.

The powder formulation was not altered and pan rotation speeds of 20-25 rpm. and tilt

angle of 40-45' were found to be optimum. The moisture content of the powder could

not exceed 30% as at higher moisture the powder balled into a large m a s .

Iodized premix wouid be required in large quantities and therefore it was essential that

the technology that was used to form these premix particles could aiso be scaled up to

meet the requirements. Two pilot scale pan agglomeration were tried in two rotating

pans of incremental sizes at the Weetabix plant in Cobourg. In the first run a 10L pan

was used with the following operating conditions:

Formulation: Feed

termination

3% Ki and 98% dextrin 1

35-45 (Variable) 11 Table 4.5 Operating parameters for 1 kg pilot scale agglorneration run

The first pilot scale run gave a yield of 45% of particles in the 3 0 0 ~ to 7 IOpm range.

There was slight browning of the premix and this is believed to be dur to Maillard

reactions as there was no loss in iodine content afier browning. The iodine content of the

premix was detemined through NAA and was found to be 1.5% I (2% KI).

The second pilot scale run in a lOOL pan was done under the following conditions:

Formulation: 1 2% Ki and 98% dextrin Feed 1 5 kg Pan angle 1 40" (Fixed) Pan rotation speed 1 30 rpm Moisture content of the powder at 1 25% termination I 1

Table 4.6 Operating parameters for 5 kg pilot scale agglomeration run

The yield of particles in the 300pm to 7 1 O p range here was found to be close to 50%.

Pan agglomeration is cheap, easy and versatile technique for making pellets. Once the

pellets are made, they need to be m e r protected through encapsulation. Encapsdation

would form a physicai bmier around the core containing the active ingredients (iron or

iodine) thus isolating them and preventing contact with moisture and other impurities in

the salt. It was discovered that the same rotating pan could be used to spray coat the

premix granules by simply substituting the water with an encapsulant solution. The

encapsulant had to be rdible, proiect the core against moisture, and should easily

decompose in the digestive tract. The solvent for the encapsulant on the other hand had

to be fairly volatile to enable quick drying between layers of coats, a slowly drying

solvent would cause the encapsulant solution to be tacky and stick the agglomerates into

bigger clurnps. The core particles also had to be insoluble in the encapsulant as the

particle integrity had to be maintained dunng spray coating.

One of the first encapsulants that was tried was shellac. The reason for this was shellac

was soluble in 95% ethanol, it is extensively used in the pharmaceutical industry for

protective coating on various dnig dosage forms, and it is accepted as a safe food

ingredient.

Zein is an alcohol soluble protein. film former. which also met the encapsulant selection

criteria as it readily forms coherent films and was also selected for the preliminary study.

Pan gnnulated KIOl premix was thus encapsulated with shellac and zein at different

levels and used as a premix in double fortified salt. The iodated premix was added to salt

with ferrous fumarate and stored in an oven maintained at 40°C and 100%RH. Samples

were taken from each of the batches at 2-week intervals for iodine content

determinations.

lodinr mtentlon of batches encapsulated with shellac

STORED AT 40*C, 100% RH Shrllac encapsufated KIO, pmmix + femus fumarate

100ppml. 10OOppmFe ---- . . - - - - - - - - - - -. - -.

Figure 4.2 Stability of shellac encapsulated K10, premix used for double fortification of salt with ferrous fumarate

From figures 4.2 and 4.3 it is evident that less than 20% iodine remained in the salt after

8 weeks of storage. The storage conditions were selected to simulate humid tropical

climates. The iodine retention in shel lac-encapsulated batc hes was similar to zein-

encapsulated batches. The retention of iodine however was not sufficient and thus a

series of experiments were performed to determine the cause of the reduction of KI03 to

free iodine. In these experiments 13% shellac-encapsulated KI03 premix was stored

under different conditions to determine the effect of storage conditions, type of salt, type

of iron on the stability of iodated salt. The effect of adding sodium hexametaphosphate

(SHMP) stabilizer was also investigated.

lodine retention of batches encapsulated with zein

STORED AT 40 O C . 100% RH Zoin &ncapsulatld WU, pmmlx + h m u s fumarate

1 OOppml, t 000ppmFe

Figure 1.3 Stability of zein encapsulated KIO, premix used for double fortification of salt with ferrous fumarate

1.3 Optimization Of Premix Formulations

Agglomeration followed by encapsulation with shellac and zein did not result in very

promising results in the preliminary tests. We could however agglornerate the particles

very easily using a rotating pan and subsequently spray coat the particles with different

encapsulants. Although the stability results were discouraging, we believed that

optimizing the formulation of the pellet would improve stability. A series of experiments

were thus designed where shellac encapsulated iodized premix was used in double

fortification of salt with different iron sources, under different conditions of storage and

in the presence of SHMP stabiiizer.

43.1 Effect Of Storage Conditions On Iodine Retention

Two batches of 13% shellac-encapsulated KI03 premix were stored at 40°C and 100%

RH. One of the batches was used as a control and was single fortified; the other baich

was double fortified with 7% shellac-encapsulated ferrous sulphate. A third batch with a

sirnilar double fortified mix was stored under room conditions. It was found that the

single fortified batch under humid conditions and the double fortified batch under roorn

conditions retained almost 80% iodine after 8 weeks of storage. The double fortified

batch stored under humid conditions retained less than 30% iodine after a similar time

period as s h o w in figure 4.4. This shows that the stonge conditions are important to

iodine stability.

Effect of Storage Conditions on lodine Retention

O 2 4 6 8 IO

Time (weeks)

+40oC. 100% RH 7% shellac enc. FeS04.7H20

A Room temp. & Humidity 7% shellac enc. FeS04.7H20

Figure 4.4 lodine retention 13% shellac-encapsulated MO, batches, single and double fortified with ferrous sulphate and stored under room conditions and 40°C-100°hRH

4.3.2 Effect of Addition of SHMP Stabilizer on Iodine Retention

Rao (Narasinga Rao. 1975) concluded that adding 7% SHMP to salt resulted in stable

double fonified salt. We intended to put that formulation to test by using a simiiar

formulation but adding the SHbP within the premix itself. 5% SHMP was added to the

ferrous sulphate encapsulant and 0.2% SHMP was dry mixed into the salt. A control

batch with only 0.2% SHMP in the salt and no stabilizer on the ferrous premix was also

prepared. Figure 4.5 gives a cornparison between iodine retention of the SHMP

stabilized batches and control batch with no stabilizer added. It can be clrarly sern that

there was no irnprovrment in the iodine retention. In all cases negligible amounts of

iodine was retained after 8 wecks of storage at 40°C and 1OO%RH.

Effect of Adding SHMP Stabilizer on lodine Retention

Time (weeks)

+40oC, 100% R H 7% shellac enc. FeS04.7H20 -

040oC, 100% RH 7% shelfac enc. FeS04.7H20 0.2% SHMP in salt

A40oC, 100% RH 10% shellac + 5% SHMP enc. F eS04.7H20 0.2% SHMP ifl salt

Figure 4.5 Cornparison o f iodine retention in batches containing 13% shellac-encapsulated KIO, premix and ferrous sulphate with different amounts of SHMP

4 3 3 Effect of Type of Iron on Iodine Retention

Ferrous sulphate is very soluble in water and also known to be more reactive than ferrous

fumarate. Ferrous fumarate was therefore tried as an active iron source. Ferrous

furnarate is recornmended over ferrous sulphate in iron supplernentation due to its highrr

stability, less palpable taste, and high bioavailabiliiy. The disadvantage in using ferrous

fumarate however, is its distinctly obvious colour. 40% fat encapsulated ferrous Fumarate

manufactured by WatsonTM was used to double fortify salt together with 13% shellac-

encapsulated KI03 Premix.

It was found that ferrous fumarate did not react significantly with the KIOi prernix and

there was no distinct colour change in the salt after 8 weeks of storage under humid

conditions. The iodine retention was close to 70% and the 30% loss in iodine was

comparable to single fonified salt. which had 20% loss under similar storage conditions.

It can therefore be concluded that ferrous fumarate resuited in a more stable double

fonified formulation and had a lower impact on iodine retention.

Effect of Type of lron on lodine Retention

Time (weeks)

A Watson enc. Ferrous furnarate (60%)

+ 7% s hellac enc. F eS04.7H20

Figure 1.6 Comparison of iodine retention between single fortified salt and double fortified salt with ferrous fumarate and ferrous sulphate respectively, stored under 40°C and 100°hRH - iodine source - 13OA shellac encapsulated KIO, premix

The best formulation at this stage was found to be with the shellac encapsulated KI03

premix and 10% encapsulated ferrous fûmarate manufactured by Watson Foods. The

ferrous Fumarate however, had a very small particle size and easily segregated.

Although the formulations did not yield stable double fonified salt, we had made

progress in some fundamental areas of double fortification:

We could agglomerate premix particles to essentially any size up to 4 mm.

We could spray coat the premix particles as long as the material dissolved in a

volatile organic solvent. We had identified methylene chloride and ethanol as

effective solvents.

The pan agglomeration and encapsulation could be scaled up to 5 kg batch sizes.

This technique was simple and highly cost efficient, an important criteria for

application of this technology in developing countries.

The stability of double fortified salt under high humidity and temperatures needed to be

solved. We believed that if a suitable encapsulant was used. which would form an

impervious layer around the active compounds and prevent moisture frorn pemtrating

into the core of the prernix, the stability of iodine and iron could be enhanced. Seven

encapsulants, which were used comrnonly in food and dmg coatings, were short-listed

and their effect on the stability of double fortified salt was studied.

1.1 Seleetion of Optimal Encapsulating Agents

Preventing moisture and impurities fiom coming into contact with iodine and iron and

preventing contact between the active ingredients would prevent them from reacting. A

suitable encapsulating agent would therefore have to be impervious to water, and form a

continuous film around the premix particle. It would also have to be digested by the

body easily to make the micronutrients bioavailable.

Seven encapsulants were tried for this study. K I 0 3 particles were agglomerated and

subsequently coated at a 40% encapsulation levels with each of the encapsulants. Fenous

fumante was also agglomerated and coated with soy stearine at 10% encapsulation

levels. Each of the encapsulated KI03 premix was used to fortib salt together with

ferrous fumarate and encapsulated ferrous furnarate respectively. Each of the 14 batches

were stored at 40°C and 100% RH for three rnonths and anaiyzed for iodine content at the

end of this time penod. Figures 4.7 and 4.8 depict the iodine retention of each of the

batches after 3 months of storage.

lodine retention of agglomerated K I 4 particles encapsulated with different

encapsubnts after 3 rnonths storage unch 40% 8 100% RH with ferrous fumarate

120 ------ ! g % lodine retention . % rnoisture

7

Figure 4.7 lodine retention o f double fortified batches with KIO, premix encapsulated by different encapsulants and unencapsuiated ferrous fumarate

lodine retenüon of agglomerated KIO, particles encapsulated with different encapsulants after 3 months storage under 4û°C % 100% RH with encapsulated

Figure 4.8 Iodine retention of dou ble fortified batches with K I 0 3 premix encapsulated by dimeren t encapsulants and encapsulated ferrous fumarate

At 40% encapsulation levels, soy stearine. palmitic acid, and polymethyl methacrylate

encapsulated batches showed incredible stability. nie 40% encapsulation level was

chosen as overkill, if an encapsulant did not work at this level it was not feasible to

pursue it. Following successfÙl identification of three possible encapsulants. soy stearine

and polymethyl methacrylate were chosen for further optimization studies. Palmitic acid

and soy stearine both contain predominantly the same chemical species in different ratios

and therefore soy stearine was chosen since it was cheaper and more easily accessible.

Polymethyl methacrylate was chosen for its film forming properties. Film coating as

opposed to layer coating requires less encapsulation.

With the two rncapsulants identitied a series of experimental combinations were

designed. We used a factorial approach involving two iodine compounds. KI and KIO,.

two encapsulants (soy srearine and polymethyl methacrylate) and two iron species

(ferrous fumarate and ferrous sulphate). Ferrous sulphate was included in the study

because it is more soluble and imparts less drastic colour change to the salt. It is

nevertheless more reactive and less stable.

4.5 Optimization of Encapsulation Level and Formulation

At 40% encapsulation levels we achieved double fortified salt which was stable for 3

months under very harsh climatic conditions. This was essentiaily done to screen out

poor encapsulating agents and to reduce the number of experimental nuis required. The

level of encapsulation on the premix particles was M e r optimized by perfoming a

series of experimental nins containing premix particles at different levels of

encapsulation. The Following combinations were studied:

5%, IO%, 20%. 30% soy stearine encapsulated agglomerated K1O3 1 iodine Premix Agglomerated KI03 in dextrin

encapsulated agglomerated KI03

Iron Premir I

Agglomented KI in dextrin l 3%, 6%, 9% soy stearine encapsulated agglomented HO3

Agglomerated ferrous fumante I

1 5%, 30% soy stearine encapsulated agglomented ferrous fumarate

Ferrous sulphate 1 3 0% soy stearine encapsulated ferrous sulphate

Table 4.7 Combinations studied for optimization of premix formulation and encapsulation level

Al1 combinations of the above iron and iodine premixes were used to double fortify salt.

Sample bags of 50g each, were stored in an oven maintained at 40°C and 100%RH for 3

months. The initial iodine content was 50ppm and iron content lOOOppm in the salt. The

moisture content, iodine content and iron content were measured at the end of the 3

months. Iron content was analyzed using the 1,lO-phenanthroline complex method and

the conversion of ferrous iron to ferric iron was noted. The samples were also

photographed to compare any colour change that had occurred.

4.5.1 Iodine Retention

There are essentially two iodine compounds, potassium iodate and potassium iodide, that

are used in iodization of salt. Potassium iodate is more favoured in developing countries

and is recommended for salts with higher rnoisture contents. KIO, however, can be

easily reduced in the presence of ferrous salts to free iodine. For optimizing the

formulation, both iodine compounds were investigated.

Figures 4.94.3 1 give a summary of the results of iodine retention. iron conversion and

the colour of the salt after three rnonths of storage under 40°C and 100% RH. The iodine

retention is irnproved by increasing the level of encapsulation on both the iodinr premix

and iron prernix. There are several observations that can be made looking at the surface

plots in figures 4.12, 4.15,4.18,4.21,4.24,4.27, and 4.30. The iodine stability increases

at increased levels of encapsuiation. This is intuitive since increased tilm thicknrss

would reduce the rate of rnoisture transport into the premix core and also provide

increased resistance to fiee iodine migration into the surrounding atmosphere from within

the core. The type of iron compound also had an impact on the iodine retention of salt,

ferrous fumarate encapsulated batches showed improved stability when compared to

fenous sulphate encapsulated batches. This was especially true for premixes containing

no3. This is because fenous sulphate is more soluble and more reactive than ferrous

+ùrnarate. The ferrous ion can easily reduce iodate to free iodine:

It was also observed that KI fortified batches had higher stability than KIO, fortified

batches. This is due to the fact that both the iodide and ferrous species are in their

reduced state. There is no oxidization agent to promote reaction. The presence of

dextrin, which is a reducing sugar, could also promote stability. Polymethyl mcthacryiate

encapsulated batches also performed beaer in tems of iodine retention and this is most

likel y due to superior film characteristics of methacry late pol ymer.

4.5.2 Iton Conversion

The trend in the conversion of iron could be correlated to the retention of iodine. It was

generally observed that there was an inverse relationship between the degree of

conversion of ferrous to femc and the retention of iodine.

Here açain, ferrous fumarate s howed better stability compared to ferrous su1 phate.

Unencapsulated Ferrous sulphate perfonned very poorly. Batches encapsulated with

unencapsulated ferrous sulphate turned yellow. had a distinct rnetallic taste and resulted

in almost total loss of iodine.

There was a correlation between the iron conversion, iodine retention and colour of the

salt. Increased iron conversion correlated with decreased iodine retention and noticeable

colour change in the sait. Salt fortified with unencapsulated ferrous sulphate also m e d

pale yellow as can be seen in figures 4.14,4.20,4.26 and 4.32.

4.53 Colour Change In Double Fortified Salt

The colour change of double fortified salt is usually the first tell tale sign of its instability.

Little or no colour change usually indicates increased stability. Double fortified salt

containing unencapsulated premix particles usually developed a purple andor yellow

colou.. The purple colour was due to the reaction between free iodine and starch. This is

highly distinguishable even under low iodine concentration and is the basis of titrimetric

methods for iodine assays. The yellow colour is likely due to die formation of femc

chloride.

There is a distinct irnprovement in colour in batches encapsulated with higher levels of

encapsulation. Ferrous fumarate also imparts an off colour to the salt. Ferrous fumarate

is brown in colour and hence salt fortified with the himarate premix could be

distinguished by distinct brown specs. Soy stearine encapsulated ferrous furnarate

however blends into white salt better since the premix is this case is somewhat grayish.

SS = Soy stearine

30% SS -Fefum

/ 15% SS -Fetum 10% SS

0% SS -Fefum % encaps.

# encaps. on bdlne 20% SS on lron

--

Figure 1.9 Retention of iodine in batches double fortified with soy stearine encapsulated KIO3 premix and soy stearine encapsulated ferrous fumarate premir after 3 months of storage at 40°C and

. - - ..

120-25

20 010-15

% conversion of Fermur to Ferric lS

r - - - - _ - a03

-. -. -

0% / , 0% SS ,; 15% SS -Fefum

,' % encaps. on lron 5%ss 10% SS -------.

20% SS ' 0% SS Jehm

% encrpr on iodine 30% SS

Figure 4.10 conversion of ferrous iron to ferric iron in batehes double fortified with soy stearine encapsulated N O 3 premix and soy stearine encapsulated ferrous fumarate premix after 3 months of storage 3t 40°C and lOO%RH.

Level of sov stearine enca~sulation on ferrous fumarate d

0% SS Fefum 15% SS Fefum 30% SS Fefum

Figure 4.1 1 Appearance of double fortified salt samples after 3 months of storage under 40°c and 100% RH.

- -

SS = Soy steanne

30% SS -FeS04

, encaps. on iron -F eSO4

l Figure 4.12 Retention of iodine in batches double fortified with soy stearine eneapsulated KIOS premix and soy stearine encapsulated ferrous sulphate premix after 3 monihs of stonge at 40°C and I OOO/o RH.

SS = Soy stearine

I Figure 4.13 Conversion of ferrous iron to ferric iron in batehes double fortified with soy stearine

t

encapsulated KI@ premix and soy stearine encapsulated ferrous sulphate premix alter 3 months of

Figure 4.14 Appearance of double fortified salt samples after 3 months of storage under 40°c and 100% RH.

100

80

X lodine 60 retention

40

% encaps. on iadine 9% MM

SS =

methy l

Soy stearine

methacry late

1

'igure -1.15 Retention of iodine in batches double fortified with polymethyl methacrylate encapsulated KIO, premix and soy stearine encapsulated ferrous fumarate premix after 3 months of storage at 10°C and 100°/'RH.

-

r--- --- _ l-- . . _ SS = Soy stearine

- - --- ._. _ MM = rnethyl rnethacrylate

-

'igure 4.16 Conversion of ferrous iron to ferric iron in batches double fortified with

1 SYO SS -Fefum W encaps. on iron

?4 encaps. on iodine 9% MM

poÏymethylmethacrylate encapsulated KIO, premix and soy stearine encapsulated ferrous fumarate premix after 3 months of storage at 40°C and lOO%RH.

LeveI of sov stearine enca~sulation on ferrous fumarate 0% SS Fefum 1 15% SS Fefum 30% SS Fefum

Figure 4.17 Appearance of double fortified salt samples after 3 months of storage under JOOc and 100°h RH.

SS = Soy

: = rnethy l

I Figure 4.18 Retention of iodine in batches double fortified with polymethyl methac-late encapsulated K I 0 3 premix and soy stearine encapsulated ferrous sulphate premix after 3 months of storage at 40°C and 100°/~RH.

r ss = SOY stearinr: 1

. 04060

Ferrous to Femc

30% SS -FeS04

% encaps. on imn 0% 2: ;4 MM

0% SS -FeSîM % encaps. on iodine '% MM 9% MM

I Figure 4.19 Conversion of ferrous iron to ferric iron in batehes double fortifîed with

I

polymethylmethacrylate encapsulated KIO, premix and soy stearine encapsulated ferrous sulphate premix after 3 months of storage at JO°C and 100°hRH.

Figure 1.20 Appearance of double fortified salt samples after 3 months of storage under 40°c and 100% RH.

1 - -

1 Level of sov stearine enca~sulation on FeSOd

SS = Soy stearine

X lodine retention 40

I

30% SS -Fefum

% encaps. on lodine 20%

25 'h conversion of Fenous to Ferric 20

15

1 O

5

O

0%

I

= Soy stearint:

1

-

Ggure 4.22 Conversion of ferrous iron to ferric iron in batches double fortified with soy stearine

Figure 4.21 Retention of iodine in batches double fortifiecl with soy stearine encapsulated KI premix and soy stearine encapsulated ferrous fumarate premix after 3 months of storage at 40°C and

encapsulated KI premix and soy stearine encapsulated ferrous fumarate premix after 3 months of storage at 40°C and 100°hRH.

15% SS Fefum :mus fumarate 30% SS Fefum

Figure 4.23 Appearance of double fortified salt sarnples after 3 months of storage under 40°c and 100% RH.

1 SS = Soy stearine

1

% bdine Mention

30% SS -FeSOs

encaps. on iron

i -FeS04

l Figure 4.24 Retention of iodine in batches double fortified with soy stearine encapsulated KI premix

I

and soy stearine encapsuiated ferrous sulphate premix after 3 months of storage ai 40°C and

SS = Soy stearine

-- - -

% encaps. on iodine 30% SS

Figure 4.25 Conversion of ferrous iron to ferric iron in batcha double fortified with soy stearine encapsulated KI premix and soy stearine encapsuhted lerrous sulphate premix after 3 months of

Figure 4.26 Appearance of double fortified salt sarnples after 3 months of storage under 40°c and 100% RH.

- Figure 4.27 Retention of iodine in batches double fortified with polymethyl methacrylate encapsulated KI premix and soy stearine encapsulated ferrous fumarate premir after 3 months of

SS = Soy stearine

MM = methyl methacrylate

Ok encaps. on iodine 9% MM

storage at 40°C and 10O0/~RH.

-

yigure 4.28 Conversion of ferrous iron to ferric iron in batches double fortified with

- -

?.- - - - - -- _ SS = Soy stearine -- .

-- -. MM = rnethyl methacplate

0 30-40 0 20-30

O r b conversion of Ferrous to F emc

30% SS -Fefum

X encaps. on iodine 9% MM

potymethylrnethacrylate encapsuiated Kt premix and soy stearine encapsulated ferrous fumarate premix after 3 months of storage at 40°C and îOOOhRH.

Level of soy stea 0% SS Fehm

le enca~sulation on ferrous fumarate 30% SS Fehm

Figure 4.29 Appearance of double fortified salt samples after 3 months of storage under 40% and 1OO0/o RH.

36 lodine retention

SS = Soy stearine

= methyl methacrylate

1 J

Figure 4.30 Retention of iodine in batches double fortified with polymethyl methaerylate encaasulated KI premix and soy stearine encapsulated ferrous sulphate prernix nfter 3 months of

SS = Soy stearine

Ferfaus to Ferric

30% SS -FeS04

W encaps. on iron

Figure 4.31 Conversion of ferrous iron to ferric iron in batches double fortified with polymethylmethacrylate oncapsulated KI premix and soy stearine encapsutated ferrous sulphate premir alter 3 months of storage at 40°C and 100°YéRH.

Level of sov stearine enca~suiation on Fesch 1

Figure 4.32 Appearance o f double fortified salt samples after 3 months of storage under 40% and 100% RH.

The results s h o w in figures 4.9-4.32 indicate that at increasing levels of encapsulation

on both iron and iodine premix, the iodine retention was increased and the conversion of

ferrous iron to femc iron was reduced. At low levels of encapsulation or under no

encapsulation of premix, there was drastic colour change in the salt. The purplish blue

colour is due to the formation of free iodine which reacts with starch to give the blue

cornplex. The yellowing of salt was only observed when ferrous sulphate was present,

this is most likely due to the formation of femc chloride.

The reaction of iron and iodine in al1 combinations which were not stable indicate that the

film around the premix particles was not entirely impervious. This problem can be

circumvented by increasing the level of encapsulation. as cm be seen by the results at

encapsulation levels of 30% and higher. The film characteristics may also improve at

production level since better processing equipment and more control would be available.

Film formulation also plays a vital role in the stability of the double fortified salt and

studies on other film forming agents is recommended.

5. CONCLUSIONS

The simuItaneous precipitation of NaCl and KI03 was not feasible in the

labontory. The iodine content and particle size could not be controlled

sufficiently to produce uniform prernix particles to be used for fortification of

salt.

Agglomeration followed by encapsulation could be easily performed in a rotating

pan. This technology is versatile. cheap and easily transferable to developing

counuies.

Production of premix particles through pan granulation could be scaled up to

1Okg without cornpromising yield and particle charactenstics.

Encapsulation of prernix particles wirh shellac and zein did not have a significant

impact on the stability of double fonified salt. In both these cases less than 20%

iodine was retained after 3 months of stonge under JOOC and 100% RH.

Soy stexine, palmitic acid and polyrnethyl methacrylate had a significant impact

on improving the stability of double fonified salt. Encapsulation by these

compounds resulted in more than 80% iodine retention in double fonified salt

after 3 months storage at 40°C and 100QRH.

Encapsulation of iron premix had a more significant impact on iodine retention

than encapsulation of iodine premix. When fenous sulphate was used the need

for encapsulation was more important than when ferrous fumarate was used.

Encapsulation with soy stearine required at least 20% encapsulation levels. in

cornparison, 6% encapsulation with polymethyl methacrylate was sufficient.

Addition of stabilizers such as SHMP, NafIC03, and Na2C03 did not have a

significant impact on the stability of salt.

It was found that KI was more stable in the presence of ferrous saits than KI03

10. Encapsulation of particles containing the active ingndients and their subsequent

addition to salt was identified as an effective method for double fortification of

salt. This approach was relatively cheap and reduced processing significantly as

only the premix particles had to be treated.

6. RECOMMENDATIONS

Pan agglomeration could be used for particle size enlargement and encapsulation. The

disadvantage with it is that the product has a very wide particle size distribution.

Encapsulation can also be performed using the same equipment however the solvent for

encapsulation in this method has to be fairly volatile to ensure quick dryng and prevent

further agglomeration. Other methods such as fluidized bed processing would allow a

wider selection of formulations to be used and may improve particle charactenstics.

Fluidized bed processing, however, is more expensive. We need to keep an open rnind

and not make a strong comrnitrnent to any specific method at this point since both simple

and complex methods of processing could be used depending on their availability in

different coun tries.

Agglomeration followed by encapsulation for added protection has shown superior

stability, more encapsulanrs need to be investigated as there may be better performing

formulationst

Medium scale pilot tests on agglomeration resulted in yields of up to 50%. Larger scale

tests with commercial equipment should result in better, more uniform film coating and

therefore higher yield and better performance.

Colour of the final pmduct will have a significant impact on its acceptability within

consumers, at this point ferrous fumante is a mon superior iron supplement but its

obvious colour may not be received by consumers. Research on different compounds

that may mask the colour is needed.

Currently, the approach is to manufacture two separate premixes for iron and iodine

respectively which are then added to salt. A premix with both the active nutrients in one

stable particle is highly desirable. This would hirther reduce processing cost, simplify

premix-salt blending, and reduce shipping costs.

The bioavailability of iron is greatly dependent on the iron compound itself, the rnatrix

within which it is supplemented, and the medium of supplementation that is used. It is

important to perform detailed efficacy studies on final formulations and there has to be

constant communication and information exchange between researchen, medical

professionals and consurnen involved.

Double fortification of salt with iodine and iron will tremendously irnprove the health and

well being of individuals. The benefits rnay not be obvious to the targeted population

immediaiety. It is therefore important that fortification programs include education and

consumer awareness into the agenda.

7. REFERENCES

Ahem, E; Swan, A; Ahern, V; The Prevalence of Iron Deficient Erythropoiesis

and Anaemia in Rural Jamaican Comrnunity. Br. J. of Haematoiogy, 22,273-280,

1972.

Anandaraman, S ; Reineccius, G; Stability of Encapsulated Orange Peel Oil, Food

Technology. 88-93. November 1986.

Anonymous. XII NACG Meeting, Combating Iron Deficiency Anemia Through

Food Fortification Technology. International Nutritional Anemia Consultative

Group, Washington, December 1990.

Anonyrnous; Handbook on Human Nutritional Requirements. Food and

Agnculture Orgaanization, Rome, ??.

Anonyrnous; www.idrc.ca/mi/idddocs/idd595.htm; D D Newsletter, Vol. 1 1, No.2,

May 1995.

Bangs. W; Reineccius, G; Characterization of Selected Materials for Lemon Oil

Encapsulation by Spray Drying. Journal of Food Science, Vo1.55, No.5, 1356- 1358,

1990.

Beard, J: Borel, M: Iron Deficiency and Thermoregulation. Nutrition Today, 41-

45, SeptemberIOctober 1988.

Bhandari, B; Dumoulin, E; Richard, H; Noleau, 1; Lebert, A; Flavor Encapsulation

by Spray Drying: Application to Citral and Linalyl Acetate. Journal of Food

Science, Vol. 57, No. 1.2 17-231, 1992.

Bjorn-Rasmussen. E; Hailberg. L; Rossander, L; Absorption of 'fortification' iron.

Br. J. Nutr., 37,375-388, 1977.

10. Callender, S; Warner, G; Iron Absorption from Bread. The Am. J. of Clin. Nutr.,

vol. 21, No. 10, 1170-1 174, October 1968.

11. Carmel, R; Weiner, J; Johnson, C; Iron Deficiency Occurs Frequently in Patients

With Pernicious Anemia. JAMA, Vol 257, No.8, February 1987.

12. Chauhan, S; Bhatt, A; Bhatt, M; Majeethia, K; Stability OF Iodised Salt with

Respect to Iodine Content, Research and Industry. Vol. 3 7 , 3 8 4 1, March 1992.

13. Clydesdale, F.M; Wierner, K.L (editon); Iron Fortification of Foods. Academy

Press Inc. Florida, 1985.

14. Conine, J; Hadley, H; Preparation of SrnaIl Solid Pharmaceutical Spheres. Dmg

and Cosmetics International, 38-4 1, April 1970.

15. Cook, J; Reusser, M; Iron Fortification: An Update. The Amencan Journal of

Clinical Nutrition, 38,648-659, October 1983.

16. DeMaeyer, E.M; Lowenstein, F.W; Thilly, C.H; The Control of Endemic Goitre.

World Health Organization, Geneva 1979.

17. Diosady, L. L.; Alberti, J. O; Venkatesh Mannar, M.G.; FitzGeraid, S.; S tability of

Iodine in iodized salt used for correction of iodine-deficiency disorders. II. Food

and Nutr. Bull., vol. 19, no. 3,340-250, 1998.

18. Diosady, L. L; Alberti, J. O; Stability of Iodine in Iodized Salt Used for Correction

of Iodine Deficiency Disorders. Final report to PATH Canada, February 1998.

19. Dobbing, J (Ed.); Brain, Behaviour, and Iron in the Infant Diet. 29-190, Springer-

Verlag, New York, Date ??.

20. Dziezak, J. D; Microenutpsulation and Encapsulated Ingredients. Food

Technology, 136-15 1, April 1988.

21. Elwood, P; Newton, J; Brown, D; Absorption of Iron from Bread. The Am. J. of

Clin. Nutr., vol. 21, No. 10, 1162-1 169, October 1968.

22. Evans, G; Mirbod, S; Jervis. R; The Volatilkation of Iodine Species Over Dilute

Iodide Solutions. The Canadian Journal of Chernical Engineering, Vol. 71-76 1-765,

October 1993.

23. Fomon, S; Zlotkin, S (Eds.); Nutritional Anemias. Nestle Nutrition Workshop

Series, Vol. 30, Raven Press, N a York, 1992.

24. Fonner, D; Banker, G; Swarbrick, J; Micromeritics of Granular Pharmaceutical

Solids 1.3 ournal of Pharmaceutical Sciences, Vo1.55, No. 2, 181-186, Febmary 1966.

25. Gillespie, S; Major Issues in Developing Effective Approaches for the prevention

and Control of Iron Deficiency. Work in Progress - Report prepared for

Micronutrient Initiative and UNICEF. September 1996.

26. Graves, R; Uses for Microencapsulation in Food Additives. Cereal Science Today,

Vol. 17. NO. 4, 107-109. April 1972.

27. Harnby, N: Edwards. M.F; Nienow, A.W (editon); Mixing in the Process

Industries. znd Ed., Buttenvonh-Heinemann, 19xx.

28. Harvey, A.E; Smart, LA; Amis, E.S; Simultaneous Spectrophotometric

Determination of IronflI) and Total Iron with lJ0-Phenanthroline, Analyücal

Chemistry. Vol. 27, No. 1, January 1955.

29. Hetzel, Basil S; The Story of Iodine Deficiency. Oxford University Press - Delhi,

1989.

30. Holman, J; Preparation of Iodized Salt For Goitre hophylaxis. Bull. World

Hedth Organization, 9.23 1-239, 1953.

31. Jackson, L; Lee. K; Microencapsulated Iron for Food Fortification. Journal of

Food Science, Vol. 56, No. 4, 1047-1050, 199 1.

32. Kapur, P; Kinetics of Granulation by Non-Random Coalescence Mechanism.

Chernicd Engineering Science, Vol. 27,1863- 1869, 1972.

33. Kawashima, Y; Takagi, H; Takenaka, H; Wet Spherical Agglomeration of Binary

mixtures, II. Chem. Pharm. Bull. Vol. 29, No. 5, 1403-1409, 1981.

34. Kelly, F; Studies on the Stability of Iodine Compounds in Iodized Salt. Bull.

World Health Organization, 9.71 7-230. 1953.

35. Kondo, Asaji; Microcapsule Processing & Technology. Marcel Dekker inc. New

York, NY, 1979.

36. estensen, H; Particle Agglomeration in High Shear Mixers. Powder Technology,

88, 197-202, 1996.

37. Kuhn. LN; Layrisse, M; Martinez, C; Walker, R.B; Observations on the Mechanism

of Iron Absorption. The Am. J. of Clin. Nutr., Vol. 21, No. 10, 1184-1 188, October

1968.

3 8. Layrisse, M; Mminez-Toms, C; Fe(1II)-EDTA cornplex as iron fortification. Am.

I. Clin. Nutr. 30: 1 166-1 174, 1977.

39. hynsse, M; Martinez-Torres, C; Roche. M; Effect of Interaction of Various Foods

on Iron Absorption. The Am. J. of Clin. Nutr., Vol. 21, No. 10, 1175-1 183, October

1968.

40. Lozoff, B; Jiminez, E; Wolf, A; Long Term Developmental Outcorne of Infants

with Iron Deficiency. The New England Journal of Medicine, Vo1.325, No. 10,687-

694, September 199 1.

41. Markel, H; "When it rains it Pours": Endemic Goitre, Iodized Salt, and David

Murray Cowie, MD. Amencan Journal of Public Health, Vol. 77. No. 2,219-229,

Febmary 1987.

42. Marks, A; Sciarra, J; Effect of Size on Other Physicai Properües of Granules and

Their Corresponding Tablets. Journal of Pharmaceuticd Sciences, Vo1.57, No. 3,

497-504, March 1968.

43. McKeman, W; Microencapsulation in the Flavour Industry. Part 1. Flavour

Industry, 596600, December 1973.

14. McKernan, W; Microencapsulation in the Flavour Industry. Part II. Flavour

industry, 7 1-74, February 1973.

45. Miranda, S; Yaeger, S; Horning in On the Best Size reduction Method. Chernical

Engineering, 102-1 10, November 1998.

46. Mutka, J; Nelson, D; Preparation of Encapsulated Flavors with High Flavor

Level. Food Technology, 154- 157, April 1988.

47. Narasinga Rao, B.S; Fortification of Salt with Iron and Iodine to Control

Anaemia and Goitre: Development of a New Formula with Good Stability and

Bioavailability of Iron and Iodine. Food and Nutr. Bull., vol. 15. no. 1,32-39, 1994.

18. Narasinga Rao, B.S; Prabhavathi, T; An In Vitro Method for Predicting the

Bioavailability of Iron from Foods. The Am. I. of Clin. Nutr. 3 1. 169-175, January

1975.

49. Nuasinga Rao, B.S; Vijayasanthy, C; Fortification of Common Salt with Iron:

Effect of Chemical Additives on Stability and Bioavailability. The Am. I. of

Clinical Nutr. 28, 1395- 140 1, Decernber 1975.

50. Pauletti, M; Amestoy, P; Butter Microencapsulation as Affected by Composition

of Wall Material and Fat. Journal of Food Science, Vo1.64, N0.3~279-282, 1999.

5 1. Perry, Robert H.; Green, Don W. (editors); Perry's Chemical Engineers'

Bandbook, 7Lb Ed. McGraw-Hiil, New York 1997.

52. Porter, S; Tablet Coating Part 1. Drug and Cosmetics International* 82-93, May

1981.

53. Porter, S; Tablet Coating Part 2. Drug and Cosmetics International, 47-, June 1981.

54. Porter, S; Tablet Coating Part 3. Drue and Cosrnetics International, 42-44, August

1981.

55. Porter, S; Tablet Coating Part 4. Dnig and Cosmetics International. 1981.

56. Reineccius, G; Carbohydrates for Flavor Encapsulation. Food Technology, 144-

149, March 1991.

57. Rosenberg, M; Talmon, Y; Kopelman, LI; Factors Affecting Retention in Spray-

Dried Microencapsulation of Volatile Materials. J . Agric. Food Chem., 38, 1288-

1294, 1990.

58. Rosenberg, M; Talmon. Y; Kopelman, LJ; The microstructure of Spray-Dried

microcapsules. Food Microstructure, Vol. 7. 15-23. 1988.

59. Rutgen. R; Longitudinal Mixing of Granular Materiai Flowing Through a

Rotating Cylinder. Chemical Engineering Science, Vo1.20, 1079-1087, 1965.

60. Sastry, K.V.S; Fueatenau, D.W; Mechanisrns of Agglomerate Growth in Green

Pelletization. Powder Technology 7,97- 105. 1973.

61. Sayers, M; Lynch, S; Charlton, R; Bothwell, T; Walker, R; Mayet, F; The

Fortification of Salt with Ascorbic Acid and Iron. British Journal of Haematology,

28,483495, 1974.

62. Shemngton, P; Liquid Phase Relationships in Fertilizer Granulation by a

Layering Process. The Canadian Journal of Chemical Engineering, Vo1.47,308-3 16,

June 1969.

63. Skoog, D; West, D; Holler, F; Fundamentals of Analytical Chemistry, 5& Ed.

Saunders College Pub. New York, 1988.

64. Sooch, S; Deo, M; Karmarkar, M; Kochupillai, N; Ramachandran, K;

Ramalingaswami, V; Prevention of Endemic Goitre with iodised Salt. Bull. World

Health Organization, 49,307-3 12, 1973.

65. Sood, S; Bane j i , L; Ramalingaswami, V; Phil, D; Geographical Pathology of Iron

Deficiency with Special Reference to India. The Am. J. of Clin. Nutr. Vol. 21, No.

10, 1149-1 155, October 1968.

66. Suwanik, R et al; Fortification of Common Salt with Iron and Iodine

Compounds..Journ~1 of Medical Association Thailand, Vo1.62, Suppl. 1,6-11, April

1979.

67. Todd, R; Microencapsulation and the Flavour Industry. The Fiavour Industry,

768-77 1. November 1970.

68. Uhl, V. W; Gray, J. B; (eds.) MIXING - Theory and Practice Vol. III. Acadernic

Press, New York, 1986.

69. Vandegaer, J.E (Ed.); Microencapsulation - Processes and Applications, Plenum

Press, New York, 1974.

70. Venkatachalarn, P.S; Iron Metabolism and Iron Deficiency in India. The Am. I. of

Clin. Nutr. 21, No. 10, 1 156- 1 161, October 1968,

7 1. Venkatesh Mannar, MG; Dunn, J.T; Salt Iodization for the Elimination of Iodine

Deficiency. ICCIDD press, Netherlands, 1995.

72. Wan, L. S. C; Jeyabaian, T; Effect of Binders on the Formation of Pellets. 1.

Water, Alcohol and Alcohol- Water Mixtures. Chem. P h m . Bull. 34 (1 1) 4744-

4752,1986.

73. Wan, L. S. C; Jeyabaian, T; Operating conditions for the formation of pellets.

Chem. P h m . Bull. 33 (12) 54495457,1985.

74. Windholz, M et ai (editon); The Merck Index, 9'h Ed. Merck & Co. hc, NJ, USA,

1976.

8. NOMENCLATURE

Abs

O C

P

DFS

E

Fe

FeFum

a 3

I

rnD

K

PPm

RH

rpm

RSD

Pm

Absorbance

Degrees Ceicius

Densi ty

Double Forti fied Salt

Porosi ty

Chemical syrnbol for iron

Short for ferrous fumarate

grands

Chemical syrnbol for iodine

Iodine Deficiency Disorden

Chemical symbol For Potassium

Parts per million

Relative humidity

Revolutions per minute

Relative standard deviation

Micrometer (lo4 meter)

9. APPENDICES

9.1 Experirnental Results

9.1 -1 Summary of results of shellac encapsulated batches

IDate: 126th Feb. 1999 - 27th AD^. 1999 1 Batch

1 I 1 1

1 15% shellac 1 1111 1001 0.51 0.241 1

# ' - - , Double fortified sait, contained -100ppm I as shellac encapsulated K103 agglomerates and 1000 pprn Fe as fenous fumarate.

Time (weeks)

O

I 1 I 1

1 (1 0% shellac 1 110) 101 1 0.51 I

1 I I 1

1 11 5Oh shellac 88 ( 1001 0.31 0.22 1

Level of encapsukttion of iodine prticie

0% shellac

Iodine (ppm)

97

2

4

1 8 10% shellac 1 111 131 35.41 1.841

lodine (%)

100

0% shellac 5% shellac 10% shellac 1 Solo shellac

0% shellac 5% shellac 10% shellac

6

%RSD

1.1

32 40 14 24

7 12

O 20

0% shellac 5% shellac 10% shellac 15% shellac

Moisture content (Oh)

0.20

30 32 36

m

30 38 12 29

7 12

O 23

5% shellac 1 0% shellac 15% shellac

r I

28 31 32

O O

13

O O

17

6.5 5.2

39.2 4.9

I J

0.56 0.55 0.43 0.33

I

39.6 6.4 -

8.1

- --

15.7

3.6 3.3 1.8

1.81 1.53 2.27 1 -65

2.29 2.24 1.93

1.41 1.37 1 38

9.1.2 Summary of results of Zein Encapsulated Batches

Levd of encapsulation %RSD Moisture

Date: Batch

26th Feb, 1999 - 27th Apr. 1999 1 Double fortified salt, contained -1 00ppm I as zein encapsulated K103 agglomerates and 1000 ppm Fe as ferrous fumarate.

O 0% zein 5% zein 10% zein

1 5% zein 2

4 10% zein 5% zein 10% zein 15% zein

63 79 99 63

0% zein 5% zein 10% zein 15% zein

121 102

1 06 112

46 47 40 40

C î 4

56 79 93 55

-- -- -- --

8

100 100 1 O1 100

5.1 0.3 1.3 1.7

0.83 0.73 1 .O2 0.93

41- 49

.)-

-- -- --

O%zein 5% zein 10% zein 1 5% zein

14.6 0.3 0.0 0.5

0.65 ,

0.43 0.38 0.40

4.3 8.3

-- -- -- --

- -- - -

0.40 0.30 0.24 0.16

39 43

1 .O 4.9

9.1.3 Sumrnory of shellac encapsulated K I 4 premix batclies stored nt diff'ercnt conditions, different iron sources, und witti ur without stabilizers.

1 Batches fonified with 13% sliellrc encapsulated KIO, premix

Room temp. & Humidity 40°C, 100% RH

7% shellac enc. FeS04.7H20

7% shellac enc. FeSO4.7H20

7% shellac enc. FeS04.7H20

5% SHMP enc. FeS04.7H20

0.2% SHMP in salt 3.2% SHMP in 5al t

110% shellac + 15% SHMP enc. FeS04.7H20 Watson enc. Ferrous fumarate (60%)

retention "-i--

20 weeks

7

9.1.4 Results of screening tests for different encapsulants

1 1 Oh lodlne retention 1

I

PEG 2000 1 901 01 -.

Encapsulant

PEG 8000

FeFum

soy stearine l ~ a l m ~ l c acid Zein Polyrnethyl methacryiate Ethyl cellulose

PEG 8000 1 931 251 16.53

Encapsulant

%RSD

--

O Month - FeFum

1 04

% moisture

5.05

3 Month - FeFum

O

3.14 5.66 3.14 2.1 1 9.43

99 90 80 87 99

Enc. FeFum

PEG 2000 Soy stearine Palmitic acid Zein Polymethyl methacryiate Ethvi cellulose

% moisture

I

93 94 34

101 24

O Month - Enc. FeFum

91 93 97 91 96

105

3 Month - Enc. FeFum

%RSD

16 80

101 60

105 66

5.89 0.00 1.10 2.60

19.00 2.09

9.1.5 Summary of results of experimental runs for optirnization of encapsulation level and type of encapsulant, iron source and iodine source (conta. ..)

encaps. on iodine premix (%)

11-2-47 KI Soy stearine 10 --- 11-2-49 KI Soy stearine 20

l ron iource

Fef um

Fefum

Fefum

Fefum

Fef um

Fef um

Fef um

Fef um

Fef um

Fefum

Fef um

Fefum

Fef um

Fef urn

Fef um

Fef um

Fef um

Fef um

Fef um

Fef um

Fefum

Fef um

Fef urn

Fef um

encaps. Type of l~eve l of

premix

3 months at 40°C & 100%RH Iodinc 1 9b lodine 1 %RSD 1 % Iron l ~ o i s t u r e

&y stearine j 0 1 6; j 9; Soy stearine

Soy stearine 15 56 92

Soy stearine 1 30 1 65 1 100

Soy stearine 1 O 1 16 1 38

Soy stearine

Soy stearine

Soy stearine

Soy stearine

Soy stearine

Soy stearine

1 ;; 1 :; Soyslearine 1 Soy stearine

Soy stearine 28 65

Soy stearine 1 15 1 32 1 76

O

15

30

O

1 5

30

1 1 I 1 1 I

Soy stearine 1 30 1 64 1 96 1 3.2 1 11 1 1.83

59

52

46

6

34

39

Soy stearlne

Soy stearine

Soy stearine

Soy stearine

Soy stearine

Soy stearine

100

95

85

14

79

87

30

O

15

30

O

1 5

Soy stearine

Soy stearine

3 1

72

73

72

61

63

O

15

76

1 O0

1 O0

1 O0

88

94

57

59

20.6

9.0

7.5

7.0

5.1

5.0

84

88

18

16

16

15

12

11

3.7

3.2

1.90

1.75

2.75

4.09

2.98

2.45

14

12

3.32

4.46

9.1.5 Surnrnary of results of experimental runs for optiniirmtion of eiicapsulation level and type of encapsulant, iron source and iodine source (Cont.. .,)

lodlne Type of Level of Iton Type of Level of lodine % lodine %RSD source encaps. encaps. on source encaps. encaps. conc. retentlon

lodine on iron (ppm 1) premix (%) premix

(%)

KI mm 9 Fefum Soy stearine 30 73 100 4.0

KI03 Soy stearine O FeS04 Soy stearine O O O -- KI03 Soy stearine O FeS04 Soy stearine 30 31 58 2.2

KI03 Soy stearine 5 FeSO, Soy stearine O O O -- KI03 Soy stearine 5 FeSO, Soy stearine 30 25 52 7.5

KI03 Soystearine 10 FeSO, Soy stearine O O O -- KI03 Soy stearine 10 FeSO, Soy stearine 30 26 54 5.1

KI03 Soy stearine 20 FeS0, Soy stearine O O O -- KI03 Soystearine 20 FeSO, Soy stearine 30 25 57 1.1

KI03 Soy stearine 30 FeS0, Soy stearine O 2 5 1.9

KI03 Soy stearine 30 FeS04 Soy stearine 30 24 60 12.6

KI Soy stearine O FeS04 Soy stearine O 7 10 5.6

KI Soy stearine O FeS04 Soy stearine 30 105 1 O0 4.8

KI Soy stearina 5 FeS0, Soy stearine O 8 11 17.3

KI Soy siearine 5 FeS0, Soy stearine 30 95 1 O0 4.1

KI Soy stearine 10 FeSO, Soy stearine O 8 12 4.6

KI Soy stearino 10 FeS04 Soy stearine 30 87 1 O0 8.7 m 1

KI 1 Soystearlne 1 20 1 FeSQ ( Soy stearine 1 O 1 43 1 67 1 10.0 I

KI Soy stearine 20 FeS04 Soy stearine 30 59 97 12.6 ~ KI Soy stearine 30 FeS0, Soy stearine O 52 91 29.1 1

I 1 I I I 1 I 1

KI 1 Soy stearine 1 30 1 FeSO, 1 Soystearine 1 30 1 51 1 88 1 13.6 1 KI03 1 mm 1 3 1 F ~ S Q 1 soy stearine 1 O 5

% lron IMolsture-

1 1 -2-1 39

conversion lcontent

1

KI03 mm 3 1 FeS04 1 Soy stearine 18 40 4.9 30 1

9.1.5 Summary of results of experimental runs for optimiuition of eiicapsulation level and type of encapsulant, iron source and iodine source (Cont.. ..)

lodine Type of Level of encaps. encaps. on

iodine prernix (%)

lron source

F&04

FeS04

FeS04

FeSO,

Soy stearine * Type of encaps.

Soy stearine

1 Soy stearine

conversion Level of encaps. on iron premix (%)

O

30

content

4.61

4.87

I 1 I I I

FeSO, 1 Soy stearine 1 O 1 8 1 12 1 15.9 1 66 1 3.54

Soy stearine

Soy stearine

Soy stearine

Soy stearine

Soy stearine

30

O

30 -

O

30

82

8

85

8

76

100

12

100

12

1 O0

7.6

4.1

8.2

4.0

3.8

15

68

13

5.00

4.33

5.55

72

14

4.65

5.50

9.2 Sample Calculations

9.2.1 Iodate Analysis

Iodate content was determined by using titrîmetnc methods. In this method the iodate ion is first reduced to free iodine by excess r in the presence of an acid. The iodine forms a purple complex in the presence of starch. The iodine is then neutralized with sodium thiosulphate until the purple colour disappean.

S tep 1: S tandardization of thiosulphate:

The strength of thiosulphate is first determined by neutnlizing a standard solution of I ~ ' with the thiosulphate solution.

For example: Vol. of thiosulphate required to neutralize 2 ml of standard I'+ solution = 5.3 1 ml Concentration of standard f + solution = 178 .O9 pg Is+/ml Strength of thiosulphate = 178.09 * 2 1 5.3 1 = 1

Iodate Analysis:

Mass of sample: 6.36g Titre vol.: 0.73mI Na2S203 Concentration of 1% (0.734 NatSr03 * 67.07 pg 1~+lrn1 Na&03)/ 636g

7.7 pg ig5+lg = 7.7 ppm I'+

7.7 ppm 1% * 214126.9 = 13 ppm MO3

* Ail lem three replicates of each titration were performed