Newsletter ARBOCEL 0607

7/29/2019 Newsletter ARBOCEL 0607

1/4

Lactose Intolerance

Lactose intolerance is the inability to digest lactose, a sugar in milk

and milk product. Lactose intolerance results from -galactosidase

(lactase) deficiency. Lactase is the enzyme necessary to metabolize

lactose. Lactose intolerance can lead to excess gas, cramping,

diarrhea, or severe allergic reaction. It is estimated that 55% of

Northern Europeans, 95% of North Americans, 90% of Asians are

lactose intolerant.

Lactose is still a commonly used excipient in pharmaceutical and

nutraceutical formulations. Alternative excipient choices preventthe need for using lactose in tablets. Alternative excipients, such as

, or , Dibasic Calcium

Phosphate (DCP)

ARBOCEL EMCOMPRESS Powdered Cellulose

are available.

Issue II/2006

Content page

Lactose Intolerance 1

About Cellulose 1

A Little Chemistry 2

Cellulose for Pharmaceutical Use 2

Types of 3

Applictions of 3

Versus Lactose in

Direct Compression Formulations 3-4

as a Filler in

Combination with 4

in a

Classical Wet Granulation 4

................................

......................................

...................................

............

.................................

.........................

........

...............

.......................

ARBOCEL

ARBOCEL

ARBOCEL P 290

ARBO CEL P 290VIVA PUR 12

ARBOCEL P 290

TechnicalNewsletterTechnicalNewsletterPage 1

Info-Hotline: + 49 (0) 79 67 / 1 52-312

ARBOCEL

ARBOCEL

ARBOCEL

ARBOCEL

is a classical excipient for pharmaceutical

formulations, which became more and more popular during the

last y ea rs. is f ro m d er ived Cellulo se, a r enewab le

sour ce from natu re .

Powdered cellulose is inert and is not metabolized by the human

body. Since it is not digested, it has no functional caloric value.

is used by formulators as an alternative to lactose.

the

lactose intolerant population continues to increase, which makes

lactose less desirable for formulation development.

1

is plant derived and no BSE/TSE risk will occur, which

had been an issue in Europe some years ago. Additionally,

ARBOCELPowdered Cellulose, Ph.Eur., USP/NF, JP

About Cellulose

Powdered cellulose is from

renewable sources.

Cellulose is the most common

organic substance on earth. It

is part of nearly all plants and

some microorganisms. In our

daily life we find cellulose in

paper, packaging materials, hy-

gienic articles, and of course in

all plant derived food, for exam-

ple fruits and vegetables. Cellu-

lose is found in many pharma-

ceutical solid dosage forms as

binder or filler.

Trees are the primary cellulose source. So the raw material for our

powdered cellolose or microcrystalline comes from different wood

sources.

1For the production of the cleaned cellulose is milled, sieved and

a dju ste d to a s pe ci al p art ic le s ize . Thi s ce llu lo se i s c alle d .

ARBOC EL

Powdered Cellulose


2/4


Issue II/2006

Info-Hotline: + 49 (0) 79 67 / 1 52-312

Fig. 2 : C C C Uellulose hain, omposed from -Glucose nits

Cellulose for Pharmaceutical Use

As ment ioned abov e, the cell ulos e is primari ly used for phar ma-ceuticals.

Native cellulose shows two different areas, crystalline and amor-

phous. The crystalline region is an area where the cellulose chains

are ordered. In the amorphous region the cellulose chains are

randomly ordered.

As a phar maceutic al exci pien t, two types of cellulose are in use,

powdered and microcrystalline. Both are derived from raw

cellulose.

During microcrystalline cellulose manufacture, most of the amor-

phous area is removed. Powdered cellulose is not chemically modified,

so amorphous material remains. During powdered cellulose manu-

facture, the raw cellulose is washed, milled, sieved and adjusted

to a specific particle size distribution.

a-

Table 1

Powdered Cel lulose 45 % crystal line 55 % amorph

Microcrystalline Cellulose 70 % crystalline 30 % amorph

crystalline

region

amorphous

region

Fig. 3 : Single Fiber

HO

H

O

HO

H

H

H

O

O OH

H

H

HO

OH

H

H

OH

O

H

OH

OHO

H

H

O

HO

H

O

HO

H

H

H

O

O OH

H

H

HO

OH

H

H

OH

O

H

OH

OHO

H

O

HO

H

O

H

OH

H

H

O

O OH

H

H

HO

OH

H

H

OH

O

H

OH

OHO

H

O

HO

HO

OH

OH

OH

O

H

H

H

H

CH

2C

C

C

C

C

H

Fig. 1 : -Glucose, the Unit for the Cellulose Chain

A Little Chemistry

bonds with each other, holding the chains firmly together and con-

tributing to their high tensile strength (Figure 2). Given a cellulose

material, the portion that does not dissolve in a 17.5% solution of

sodium hydroxide at 20 C is cellulose, which is true cellulose,

primarily used for pharmaceuticals; the portion that dissolves and

then precipitates upon acidification is -cellulose; and the portion

that dissolves but does not precipitate is -cellulose. For humans

this material is absolutely inert, not absorbable and noncaloric.

Additio nall y, the cell ulos e is not a good medi um for

microorganisms which decreases the risk of microbial spoilage.

a

g

-

Cellulose (C H O )n is a long-chain polymeric polysaccharide carbo-

hydrate, of monomers

1 > 4 glycosidic bonds by conden-

sation. This forms a straight chain polymer which molecule adopts

an extended rod-like conformation. The degree of polymerization

gives the average number of the residues in the chain. In microfibrils,

the multiple hydroxyl groups on the glucose residues form hydrogen

6 10 5

-gl uco se ( Fi gu re 1) . C el lu lo se ( -gl uco se)

are linked together through


3/4Info-Hotline: + 49 (0) 79 67 / 1 52-312


Issue II/2006

Types of ARBOCEL

Table 2

Form Powder Powder Granulate

Particle Size 60 m 80 m 150 m

Bulk Density 0,22,g/ml 0,30 g/ml 0,35 g/ml

An gl e of Re po se 62 49 36

M 80 P 290 A 300JRS supplies two types of powder and a granulated material

(Table 2). Type M 80 is designed for wet granulation. P 290

can be used for direct compression in combination with other

binders, e.g. , or

. The A 300 with a particle size of 150 m is

recommended for capsule filling due to improved flow.

VIVAPUR 102

VIVAPUR 12

Microcrystalline Cellulose

The differe nces between the powd er and the granulat ed mate rial

can be seen in the SEM pictures. Both, the M 80 (Figure 4) and

the P 290 (Figure 5) have a fine, fibrous structure, while the

Fig. 5 : ARBOCEL P 290 Fig. 6 : ARBOCEL A 300

The comp ress ion profile shows the comp ress ibi lity of the 3

types. The M 80 and P 290 provide more robust tablets

than A 300, which is recommended for capsule filling (Figure 7).

ARBOCEL

Applications of ARBOCEL

0 25

180

160

140

120

100

80

60

40

20

0

5 10 15 20

Har

dness

[N]

Compression Force [kN]

Fig. 7 : Compression Diagram of the 3 Grades.ARBOCEL

ARBOCEL P 290

ARBOCEL A 300

ARBOCEL M 80

ARBOCEL P 290 Versus Lactose in Direct Compression Formulations

Table 3 : Parameters of Placebo Tablets Compressed with Lactose DC or resp.ARBOCEL

Compressibility of Powered Cellulose

ARBOC EL

EMCOMPRESS

49.5

50.0 %

M ag ne si um S te ar at 0 .5 %

Powdered Cellulose

CalciumHydrogen Phosphate

A compari son between tablets compres sed from a MCC / lact ose

blend vs. tablets compressed from a MCC / powdered cellulose

blend (Table 3). There is no significant difference in tablet proper-

ties, which infers that lactose can be substituted by cellulose with-

out issue.

A 300 (Figure 6) is comp acted to larger, some times round shap ed

particles. It is obvious that P 290 has more binding properties and

A 300 shows bett er flow abil ity.

50 % 50 %

50 % Lactose DC 50 %

VI VA PU R 10 2 VI VA PU R 102

AR BO CE L P2 90

(Microcrystalline Cellulose) (Microcrystalline Cellulose)

(Powdered Cellulose)

Compression Force 6,0 kN 6,0 kN

Hardness 6,9 kp 6,8 kp

Table t We ig ht 43 6 mg 42 3 mg

Rel.stand.dev 2,1 % 2,3 %

Fig. 4 : ARBOCEL M 80


4/4


WORLDWIDE HEADQUARTERS USA+Canada

JRS PHARMA GMBH+CO.KG JRS PHARMA LP, USA

JRS PHARMALEADINGTHE WORLDIN EXCIPIENTSA Member of the JRS Group

2981 Route 22, Suite 1Patterson, NY 12563-2359

Toll-Fr ee: (800 ) 431- 2457Phone: (845) 878-3414F ax: (84 5) 8 78 -3 48 4E-mail: [email protected], www.jrs.de

Holzmhle 1D-73494 Rosenberg (Germany)Phone: + 49 (0) 79 67 / 1 52-0Fax: + 49 (0) 79 67 / 1 52-345E-mail: [email protected],www.jrs.de

Customer Service:Customer Service: ++49 (0) 7967 / 152-312 (845) 878 3414

Issue II/2006

Table 5: Ambroxol Formulation with ARBOCEL P 290

Table 4 : Ascorbic Acid Formulation Where Lactose is Replaced by ARBOCEL P 290

Am br ox ol HC l 30 .0 mg 20 .0 %

6 9 3 m g 4 6 2 %

4 6 2 m g 3 0 8 %

3 0 mg 2 0 %

1 5 mg 1 0 %

Tab le t Weig ht 15 0 mg

Diameter 8 mm

Compression Force 12.5 kN

Hardness 6.4 kp

Disintegration Time 15 sec

VI VA PU R 12 . .

AR BO CE L P 29 0 . .

VI VA SO L . .

PRUV . .

(Microcrystalline Cellulose)


(Croscarmellose Sodium)

(Sodium Stearyl Fumarate)

Table 6: Piroxicam Formulation with ARBOCEL P 290

Way of preparation : Piroxicam, and

were granulated using an 20% ethanolic povidone solution.

, Aerosil and magnesium stearate were then added and

mixed for 5 minutes. The blend was compressed at a compaction

force of about 17.5 kN (Table 6).

VIVAPUR 101 ARBOCEL P 290

VIVASOL

ARBOCEL P 290 in a ClassicalWet Granulation

A formulation with as a plant-derived filler is shown

(Table 5). provides the hardness and the flowability.

adds to the hardness as well.

ARBOCEL P 290

VIVAPUR 12

ARBOCEL

ARBOCEL P 290VIVAPUR 12

as a Filler inCombination with

In an ascorbic acid formulation, the lactose was replaced by

(Table 4). Hardness vs. compression force is the same in both

tablets formulations. This indicates that can be used

as an alternativ to lactose. The lactose-free version demonstrates

better disintegration time.

ARBOCEL

P 290

ARBOCEL P 290

Disclaimer:

The information provided in this brochure is based on thorough research and is believed

to be completely reliable. Application suggestions are given to assist our customers, but

are for guidance only. Circumstances in which our material is used vary and are beyond

our control. Therefore, we cannot assume any responsibility for risks or liabilities, which

may result from the use of this technical advice.

ARBOCEL P 290 Versus Lactose in DirectCompression Formulations

As co rb ic Ac id 50 .0 % 50 .0 %

2 4 5 % 24 5 %

24 5 %

Lactose 24.5 %

Magnesiumstearate 1.0 % 1.0 %

Table t Weig ht 20 0 mg 20 0 mg

Diameter 10 mm 10 mm

Compression Force 11.0 kN 11.4 kN

Hardness 10.8 kp 10.7 kp

Disintegration Time 50 sec 62 sec

VI VA PU R 10 2 . .

AR BO CE L P 29 0 .



Piroxicam 10.00 mg 6.7 %

7 6 8 0 m g 5 1. 2 %

5 1 2 0 m g 3 4. 1 %

3 .00 m g 2 .0 %

PVP Kollidon 25 7.50 mg 5.0 %

Magnesium Stearate 0.75 mg 0 .5 %

Fumed Silica 0.75 mg 0.5 %

Tab le t Weig ht 15 0 mg

Diameter 8 mm

Compression Force 17.5 kN

Hardness 5.8 kp

Disintegration Time 39 sec

VI VA PU R 10 1 .

AR BO CE L P 29 0 .

VI VA SO L



(Croscarmellose Sodium)

4291E3

.00609KE

Newsletter ARBOCEL 0607

Documents

Transcript of Newsletter ARBOCEL 0607