ALCOHOL IN PHARMACEUTICAL PRODUCTS

DZULKIFLY MAT HASHIM

dzulkifly@gmail.com

HALAL PHARMACEUTICAL FORUM, PULLMAN BANGSAR HOTEL, 29 Sept 2018

CONTENT OF THE DECISION (SIGHAH) ON ALCOHOL IN FOOD & DRINK,

PERFUMES AND PHARMACEUTICAL PRODUCTS (2011)

FATWA (LEGAL RULING) ON ALCOHOL IN FOOD & DRINK, PERFUMES AND PHARMACEUTICAL PRODUCTS (2011)

7.

Medicines and perfumes containing

alcohol as a solvent is not impure (Najs) and

are permissible provided such alcohol is not extracted from the

winemaking process

1.

Every wine contains alcohol. However, not all alcohol are intoxicants.

Alcohol that is extracted from the winemaking

process is ruled as prohibited (haram) and

impure

2.

Alcohol that is not produced through the winemaking process is

not ruled as impure (Najs), but is prohibited (haram) to be consumed in its original form as it is

poisonous and can kill

3.

Light beverages processed/made not for

the purpose of producing wine and containing

alcohol below the level of 1% v/v are permissible

to be consumed

4.

A beverage made with the intention and method of

producing wine, regardless of whether its alcohol content is high or low or whether their alcohol content removed by

distillation or evaporation, its consumption is prohibited

5.

Food or beverages containing natural

alcohol such as fruits, nuts, grains or their juices,

or alcohol that incidentally forms during the production process of certain food or beverages is not considered impure and is permissible to be

consumed

6.

Food or drinks with flavouring or colouring that contains alcohol for stabilisation purposes are permissible to be consumed

provided that the alcohol is not produced from the winemaking

process, the quantity of such alcohol in the final product is not intoxicating and the alcohol level

does not exceed 0.5%

The National Fatwa Council for Islamic Religious Affairs Malaysia discussed the issue of alcohol in food, drinks, perfumes and medicines on the 14th to 16th July, 2011 and reached the following decisions:

7. Medicines and perfumes containing alcohol as a solvent agent are not impure (Najs) and are

permissible provided such alcohol is not extracted from the winemaking process.

ALCOHOL IN PERFUMES AND PHARMACEUTICALS

What should be the alcohol content from a halal (Shariah) standpoint for

pharmaceutical products?

• Malaysia (through any existing regulation on pharmaceutical products) does

not have a standard on the shariah compliant (permissible) level of alcohol in

pharma products

• Alcohol is permissible to be used in pharma products as long as it is not

extracted from a brewery process (ethanol in alcoholic beverages may be

obtained or separated through distillation or vacuum evaporation)

• The question is whether alcohol is a necessary excipient in pharma products?

ALCOHOL CONTENTOF SOME PHARMAPRODUCTS

MEDICATIONS CONTAINING

ALCOHOL

QUESTION :

SHOULD THE FDA PROPOSAL BE THE BASIS OF A HALAL

COMPLIANT LEVEL FOR PHARMA PRODUCTS?

Should the FDA

proposal be a basis?

FROM A HALAL (SYARIAH) STANDPOINT, WHAT SHOULD BE THE APPROPRIATE

ALCOHOL LEVEL FOR PHARMACEUTICAL PRODUCTS?

• Pharmacists and Islamic scholars can establish guidelines

on the alcohol content of pharma products

• Need to consider whether the excipient (amount of

ethanol as a solvent) is really necessary deliver the right

efficacy of the pharma product

• Considerations are based on safety and shariah compliant

factors of pharma products

QUESTION : WHAT IS THE BASIS OF THE GUIDELINE ON ALCOHOL IN

FOOD AND DRINK?

DEFINITION OF KHAMR (ARAK or INTOXICATING DRINK)

THE SYARIAH DEFINITION OF KHAMR

(INTOXICATING DRINK)

حرامخمروكلخمرمسكركل

“Anything that intoxicates is Khamr and all Khamr

(intoxicant) is haram (prohibited)"

(Hadith in Muslim)

MEANING OF KHAMR

USE OF KHAMR : Whether in Small or Large Quantity are Equally Prohibited

The majority of Islamic scholars by consensus (ijma‘) consider kham’r

as prohibited even though it is consumed in small quantity, whether it

will cause intoxication or otherwise

ما أسكر كثيره فقيله حرام

“Anything that intoxicates, whether it is consumed in large quantity or small quantity is (still) considered as haram"

(Hadith narrated by Nasa 'i and Abu Daud)

ن عمل الشي يا أيها الذين آمنوا إنما الخمر والميسر والنص طان اب والزلم رجس م

فاجتنبوه لعلكم تفلحون

“O You who believe, verily kham’r and gambling and idol worship and and

chance of fate using arrows are deeds which are abhorred and deeds of the

evil one. Avoid them so that you may be successful”.

(Surah Al-Maidah: verse 90)

THE PROHIBITION OF KHAMR IN AL-QUR'AN

حراممسكروكلخمرمسكركل

“Anything that intoxicates is Khamr and all Khamr (intoxicant) is haram

(prohibited)"

(Hadith in Muslim)

MEANING OF KHAMR

THE USE OF KHAMR

The majority of scholars by consensus (ijma‘) consider khamr as

prohibited even though it is consumed in small quantity, whether it

will cause intoxication or otherwise

ما أسكر كثيره فقيله حرام

“Anything that intoxicates, whether it is consumed in large quantity or

small quantity is (still) haram"

(Hadith narrated by Nasa 'i and Abu Daud)

ر والنصاب والزلم رجس يا أيها الذين آمنوا إنما الخمر والميس

ن عمل الشيطان فاجتنبوه لعلكم تفلحون م

“O You who believe, verily khamr and gambling and idol worship and

and chance of fate using arrows are deeds which are abhorred and

deeds of the evil one. Avoid them so that you may be successful”.

(Surah Al-Maidah: verse 90)

THE PROHIBITION OF KHAMR IN AL-QUR'AN :

DEFINITION OF ETHANOL , ALCOHOLIC DRINK

AND INTOXICANTS

DEFINITION OF KHAMR (INTOXICATING) AND INDUSTRIAL ETHANOL

INDUSTRIAL ALCOHOL

• Not an impurity, not

a product of alcoholic

beverage

• Solvent and cleaning

agent

• Produced by

fermentation of

agriculture biomass

• Synthetically

produced from by-

product of petroleum

refinery

ETHANOL

KHAM’R

Liquid

Intoxicatan

t

Najis

(Najasa)

• Intoxicating

• Product of

fermentation of

fruits and

cereals

• Ethanol is the

component

causing

intoxication

Filth or

impurity

(Rijsun)

DEFINITION OF INTOXICATING DRINK IN MALAYSIA FOOD REGULATIONS (1985)

DEFINITION OF ALCOHOLIC BEVERAGE IN FOOD REGULATIONS (1985) :

REGULATION 361(1-2)

SYARIAH CRIMINAL ENACTMENT (1995), STATE OF SELANGOR

SYARIAH CRIMINAL ENACTMENT (1995)

SECTION 18(1), STATE OF SELANGOR

DEFINITION OF ALCOHOL AND ETHANOL

• From a chemistry perspective, “Alcohol” refers to any compound

with a hydroxyl group (–OH)

• Examples:

➢ isopropanol

➢ methyl alcohol (methanol)

➢ butyl alcohol (butanol)

➢ propyl alcohol (propanol)

➢ sorbitol

CHEMICAL DEFINITION

CHEMICAL AND STRUCTURAL PROPERTIES OF ETHANOL

• Chemical name = Ethyl Alcohol

• Colourless

• Volatile

• Flammable

• Soluble in water

• Intoxicating

• Poisonous

INDUSTRIAL ALCOHOL

• Synthetic Alcohol

– Chemically Synthesized from Ethylene

– Process:

1. Indirect hydration through addition of sulfuric acid

2. Direct catalytic hydration of ethylene

• Agricultural Alcohol

– Derived from Biological Fermentation Process of Carbohydrate Source

• Fermentation of Sugar

• Fermentation of Starch

DIRECT CATALYTIC HYDRATION OF ETHYLENE

» Ethylene is olefin produced from ethane-propane cracking.

» Using phosphoric acid (H3PO4) as catalyst

» Hydration occurs in gaseous phase

H2C=CH2 + H2O C2H5OHethylene ethanol

[H+]

SYNTHETIC ALCOHOL

PRODUCTION OF INDUSTRIAL ALCOHOL

INDUSTRIAL ALCOHOL

INDUSTRIAL PRODUCTION OF ETHANOL FROM CORN

(Courtesy of Fermpro Sdn Bhd.)

DENATURED ALCOHOL

• Ethanol produced either from petrochemical oragricultural feedstock to which a denaturant,such as methyl alcohol, pyridine, denotoriumhas been added.

• The word denatured refers to the removal of aspecific property to make it poisonous andundrinkable , as opposed to changing the ethanolchemically

• Other denaturants for industrial application:– Isopropyl alcohol, gasoline, methyl ethyl ketone,

chloroform, methyl-isobutyl ketone, denotoniumbenzoate.

APPLICATIONS OF ETHANOL

• Alcoholic beverage (present in)

• Solvent

• A chemical for laboratory use

• Fuel

• Industrial use

– Flavor carrier for the food industry

– A solvent for extraction of coloring compounds

– Solvent for extraction in pharmaceutical products

– Diluent for fragrance essences in perfumes

INTOXICATION

MODEL FOR METOBOLISM AND INTOXICATION OF ETHANOL

• Introduced by Erik Matteo Prochet Widmark

(1889 – 1945), a medical Professor and

physiology expert from Sweden

• Wrote the book, Principles and Applications

of Medico-legal Alcohol Determination

(1932)

WIDMARK’S FORMULA

Where:

N = No of drinks

W = Body weight (oz.)

r = Distribution volume = Widmark factor (L/kg)

Ct = BAC (for time) (kg/L)

β = Kadar uraian (Kg/L/hr)

t = time of drinking (jam)

d = ethanol density = 0.82 (oz./fl.oz.)

Z = amount of alcohol in a drink (fl. oz.)

WIDMARK’S EQUATION

Rearranging Widmark formula :

Ct = Blood Alcohol Concentration (BAC) (kg /L atau %)

Reference : Gullberg, R.G. (2007). Estimating the uncertainty associated with Widmark’s equation as commonly applied in

forensic toxicology. Forensic Science International (2007) 172, 33-39.

*BAC (%) STAGE CLINICAL SYMPTOMS

0.01-0.05 Sub-clinikal • Normal behaviour

0.05-0.12 Euphoria

/happy

- Increased confidence, like to socialize, more talkative, sensory motor

disturbed, lack in attentiveness

- Loss of self control, decreased ability to make good judgement

0.09-0.25 Excitement

/extremely happy

- Emotionally unstable, loss of judgement

- Disturbed perception, memory and speech

- Loss of balance on standing, loss of self control, hallucination,

headache, vision affected

0.18-0.30 Confusion

/confused state- State of confusion, emotionally disturbed, vision affected, weak,

speech slurred, muscular movement uncoordinated

0.25-0.40 Stupor

/pressured

- Motor function affected, cannot respond to stimulation, cannot stand

and walk

- Cannot control bowel function, vomiting, sleepy

0.35-0.50 Coma- Unconscious, abnormal body temperature, uneven blood flow and

respiration

- Can cause death

> 0.45 Death - Dead

RELATIONSHIP BETWEEN BLOOD ALCOHOL CONTENT (%) AND STATE OF INTOXICATION

• Ethanol passes through the mouth and through the

esophagus to the stomach and to the small intestine.

• Ethanol can be absorbed at any point of these body

parts. It is estimated that ethanol is absorbed

(estimated at 20%) and small intestine (estimated

at 80%).

• Alcohol is then absorbed by the bloodstream

• Ethanol reaches the brain via the blood

MECHANISM OF ABSORPTION OF ETHANOL BY THE BODY

KINETICS OF INTOXICATION

WIDMARK’S FORMULA

• BAC will depend on state of fullness or hunger.

• BAC is doubled 2 in an empty stomach

INTOXICATING POTENCIES OF VARIOUS ALIPHATIC ALCOHOLS

APPLICATION OF WIDMARK FORMULA IN

ESTIMATION OF STATE OF INTOXICATION

10

100

1000

10000

100000

0.01 0.05 0.1 0.5 1

VOLUME (in ml) OF DRINK CONSUMED IN 1 HOUR BEFORE

REACHING THE STATE OF INTOXICATION(BAC = 0.05 % W/V) *

Volume

(ml)

Alcohol (%)

Assumptions

▪ Gender = Female

▪ Weight = 55kg

▪ Time = 1 hour

▪ Faktor Widmark = 0.55

* Based on the Widmark Formula

** The kidneys can optimally process around 800 - 1000 ml in 1 hour

**

AMOUNT CONSUMED BEFORE REACHING STATE OF INTOXICATION (BAC = 0.05% w/v)

ALCOHOL

CONTENT(%)VOLUME (ml)

NO. OF

GLASSESCOMMENT

0.01 243,000 900 Not possible (X)

0.05 54,000 200 Not possible (X)

0.1 24,300 90 Not possible (X)

0.5 5,130 19 Not possible (X)

1.0 2430 9Possible (/) / Not

possible (X)

2.0 1350 5 Possible (/)

Volume of one glass (mug) = 270 ml

Volume of one glass (ordinary) = 165 ml

MALAYSIA MALE

• Average weight : 70 kg

• Average height : 165 cm

• Widmark factor (r) = 0.71

AMOUNT CONSUMED BEFORE REACHING STATE OF

INTOXICATION (BAC = 0.05% w/v)

ALCOHOL (%) VOLUME (ml)NO. OF

GLASSES*COMMENT

0.01 405,000 1500 Not Possible (0)

0.05 81,000 300 Not possible(0)

0.10 40,500 50 Not possible (0)

0.50 8,100 30 Not possible (0)

1.00 4,050 15 Not possible (0)

2.00 2,160 8 Possible(1)

5.00 810 3 Possible (1)

*1 Glass = 270ml

405,000

81,00040,500

8,1004,050

2,160

1

1,000

1,000,000

0.01 0.05 0.1 0.5 1 2

VO

LU

ME

(m

l)

ALCOHOL CONTENT (%)

VOLUME (ml) CONSUMED BEFORE STATE OF

INTOXICATION (BAC = 0.05% w/v)

MALAYSIA FEMALE

• Average weight : 50 kg

• Time = 1 jam

• Widmark factor (r) = 0.55

VOLUME CONSUMED BEFORE REACHING STATE OF

INTOXICATION (BAC = 0.02% W/V)

ALCOHOL

CONTENT(%)VOLUME (ml)

NO. OF

GLASSES*COMMENT

0.01 135,000 500 Not Possible (0)

0.05 24,300 90 Not possible(0)

0.10 13,500 50 Not possible (0)

0.50 2,430 9 Not possible (0)

1.00 1,350 5 Not possible (0)

2.00 540 2 Possible (1)

5.00 270 1 Possible (1)

305,100

62,10031,050

6,2103,240

1,620

1

1,000

1,000,000

0.01 0.05 0.1 0.5 1 2

VO

LU

ME

(m

l)

ALCOHOL CONTENT (%)

AMOUNT CONSUMED BEFORE REACHING THE STATE OF

INTOXICATION (BAC = 0.05% w/v)

MALAYSIA FEMALE

• Average weight : 60 kg

• Average height : 153 cm

• Widmark factor(r) = 0.63

ALCOHOL

CONTENT (%)VOLUME (ml) NO. OF GLASSES COMMENT

0.01 305,100 1130 Not possible (0)

0.05 62,100 230 Not possible (0)

0.10 31,050 115 Not possible (0)

0.50 6,210 23 Not possible 0)

1.00 3,240 12 Not possible/Possible

(0)

2.00 1,620 6 Possible (1)

5.00 675 2.5 Possible (1)

1 Glass = 270 ml

Amount of drinks consumed (ml) before reaching the state of intoxication

(BAC = 0.05% w/v)

305,100

62,10031,050

6,2103,240

1,620

1

1,000

1,000,000

0.01 0.05 0.1 0.5 1 2

VO

LU

ME

(m

l)

ALCOHOL CONTENT (%)

AMOUNT TAKEN IN 1 HR BEFORE REACHING STATE OF

INTOXICATION (BAC = 0.05% w/v)

0

0.01

0.02

0.03

0.04

0.05

0.06

0 5 10 15 20

BA

C (

%)

NUMBER OF GLASS (x270 ml)

BLOOD ALCOHOL CONTENT ('REASONABLE MAN')

INCREASE IN BAC FOR MALE DUE TO CONSUMPTION OF DRINK CONTAINING ALCOHOL

0

0.01

0.02

0.03

0.04

0.05

0.06

0.07

0.08

0 2 4 6 8 10 12 14 16

BA

C (

%)

NO. OF GLASS (x 270 ml)

BLOOD ALCOHOL CONTENT(%)

Lelaki

Wanita

COMPARISON IN THE INCREASE OF BAC IN MALE AND FEMALE DUE TO

CONSUMPTION OF DRINK CONTAINING ALCOHOL

0

0.01

0.02

0.03

0.04

0.05

0.06

0.07

0.08

0 2 4 6 8 10

BA

C (

%)

BILANGAN GELAS (x270 ml)

COMPARISON OF INCREASE IN BAC DUE TO ACUTE INTAKE AND

PROPORTIONALLY FOR FEMALE

Secara Akut

Secara Berkadar

COMPARISON OF INCREASE IN BAC DUE TO ACUTE AND PROPORTIONAL INTAKE

FOR FEMALE

• Kandungan alkohol =

1%

• Isipadu = 1000ml

• Akut = Ambil

mendadak (0 jam)

• Berkadar = Ambil

dalam 1 jam

0

0.01

0.02

0.03

0.04

0.05

0.06

0.07

0.08

0.09

1 1.5 2 2.5 3

BA

C (

%)

ALCOHOL CONTENT(% v/v)

EFFECT ON THE BLOOD ALCOHOL CONTENT (BAC)

Wanita

Lelaki

COMPARISON BETWEEN MALE AND FEMALE IN THE INCREASE OF BAC DUE TO

ACUTE INTAKE OF A DRINK CONTAINING ALCOHOL

• Alcohol content = 1%

• Volume = 1000ml

• Acute= immediate

intake (0 hr)

• Proportional = taken

in 1 hour

ISSUE # 1

If ethanol is produced by the same process as in winemaking

(fermentation), does it make it (ethanol) non-halal?

❑ Fermentation is a preservation process which is ordinarily involved to produce

various food products from various botanical sources such as cereals (sour

dough) , fish (budu or fermented anchovies), fruits (tempoyak or fermented

durian), shrimps (belacan & cincalok) and legumes (soya sauce)

❑ The fermentation process is not necessarily just to produce product for the

purpose of intoxication (alcoholic beverage)

❑ The halal status of a product will depend on the objective (niyyah) for which

the product is produced (Al Umur Bi Maqasidiha) and also on how it is going

to be used.

ISSUE # 2

Is the ethanol produced as an industrial alcohol the same that is

that is produced in an alcoholic beverage (khamr)?

❑ Some misunderstanding occurred when the original term in Arabic which is

khamr (Arab) to alcohol (in English)

❑ The meaning of alcohol has a wider meaning and connotation and not only

limited to ethanol or the alcoholic beverage only

❑ The halal status will depend on the intention or the purpose of the product

(Al Umur Bi Maqasidiha).

❑ Ethanol does not necessarily mean khamr although the intoxicating

constituent of khamr is ethanol.

ISSUE #3

What is the amount of alcohol that can be allowed to be present in

food and drink for it to be considered as halal compliant ?

❑ To benchmark the permissible level of alcohol in food and drink at a level between

0.01% hingga 0.05% is not practical as it was found that the non-alcoholic products

have alcohol levels more than 0.01%.

❑ It is found that there are some products where the level of alcohol was found to be

higher than 0.1%) such as energy drinks, cultured drinks and vinegar but does not

bring about the possibility of intoxication.

❑ There are ‘Intermediate products’ such as in flavours and colours which may have

higher alcohol contents but these are often diluted when they are used in the final

product and the level of alcohol is around 0.01%. They are not consumed directly in

its original form.

ISSUE # 4

Will adding khamr in the preparation of food and drink be permissible? Will the

constituent be totally evaporated off?

❑ It is not permissible to add khamr in any food/drink preparation

as adding it with khamr is considered as a contaminant.

❑ Khamr (residues) will remain to be present even food

preparations even after they have been vigourously cooked or

heated for a long time.

ISSUE #5

Can the “medico-legal principles of intoxication” be applied as the basis to

determine the level of alcohol in food and drink ?

❑ The basis of deciding the permissible level of alcohol in food and drink must

be on a clear basis and not to be decided randomly

❑ The “Principles of intoxication” that is used as a basis in ‘medico-legal’ cases

related to drink-driving can be used to assist the decision in determining the

permissible level of alcohol in food and drink

❑ It is suggested that a maximum level of 1% v/vis adopted as the permissible

level of alcohol in food and drink

ISSUE #6

What is the amount of alcohol that is permissible to be present in fermented food

and drink?

❑ The maximum amount of alcohol in nabidh from dates on the 3rd day is 0.06%.

❑ Tapai is found to have an alcohol content of higher than 1%, but no cases of

intoxication has been reported thus far.

❑ The influence of density and the presence of a solid matrix may bring about in

dampening the absorption of alcohol by the human digestive system this has to be

investigated further.

❑ The levels of alcohol in nira (Arengata pinata) and nipah (coconut) palm saps are

high and also need further investigations .

FROM A HALAL (SYARIAH) STANDPOINT, WHAT SHOULD BE THE APPROPRIATE

ALCOHOL LEVEL FOR PHARMACEUTICAL PRODUCTS?

• Pharmacists and Islamic scholars can establish guidelines

on the alcohol content of pharma products

• Need to consider whether the excipient (amount of

ethanol as a solvent) is really necessary deliver the right

efficacy of the pharma product

• Considerations are based on safety and shariah compliant

factors of pharma products

QUESTION : WHAT IS THE BASIS OF THE GUIDELINE ON ALCOHOL IN

FOOD AND DRINK?

CONCLUSION

❑ A scientific and shariah-based approach is used to assist in the

determination of level of alcohol in food and drink

❑ The ’medico-legal’ (medico-legal principles) has been utilised to

determine the level of alcohol in food and drink

❑ To overcome uncertainties and proper cordination of the levels of alcohol

in various products is pertinent in helping the expansion of the halal

industry.

❑ 1% (v/v) is determined as the maximum level of alcohol in food products

produced through natural fermentation.

Thank You