VERITAS PHARMACEUTICALS LIMITED,

Muradpur, Vannara, Mouchak, Gazipur, Bangladesh

ffiritas
STANDARD TEST PROCEDURE

Name of Material: MICROCRYSTALLINE CELLULOSE (Avicel Ph 102) BP/EP

Document No.: TP/1 1 03005/01 lssue Date : 02Feb 2014

Version No.:01 Superseded doc. No.: VRME/M/07 121005 Review Date : 01 Feb 2017

Approval of Current Version of the Document

Name Job Title Signature & Date

Md, Monjur Rahman Quality Control Officer tzrar^.dv

Prepared by
ular/|4^
Agreed by Md. Tarikul lslam Bossunia Asst. Manager Quality Control 'Whlr/r1
Approved by Md. Moniruzzaman Quality Assurance Manager srffi,fl.,y

CONTENT

1. Description

2. Solubility

3. ldentification

4. pH

5. Conductivity

6. Ether-solublesubstances

7. Water-solublesubstances

B. Heavy metals

9. Loss on drying

10. Sulphated Ash

11, Microbiological Contamination/g

12. Bulk Density : Without Tapped

13. Particle size

14. Revision History

DISTRIBUTION LIST

QC Laboratory 0'l

This document is Effective from ihe Date of the Approval.

WITHOUT PERMISSION FROM HEAD OF QUALITY ASSURANCE OR HIS/HER DELEGATE, COPY OF THIS DOCUMENT IS

STRICTLY PROHIBITED

Page 1 of 6
 VERITAS PHARMACEUTICALS LIMITED,
Muradpur, Vannara, Mouchak, Gazipur, Bangladesh
ffieritas
STANDARD TEST PROCEDURE

Material Name: MICROCRYSTALLINE CELLULOSE (Avicel Ph 102) BP/EP

\9
Version: Prepared BV' Approved ,t,$,51r
Doc. No.: TP/1 1'13005/01 01
fflo
1. Appearance

Procedure:

Take about 1 gm of sample in a watch glass and observe for its physical appearance, color, etc. using a white background.

Acceptance criteria: White or almost white, flne or granular powder.

2. Solubility

Procedure: Take sample in test tube, add sufficient measured amount of solvent as given following below and shake 1 to 3
minutes.

Soluble : should be clear solution

Table -1:
Descriptive term Approximate volume of Solvent in milliliters per gram of solute
Very soluble Less than I
Freely soluble From 1 to 10

Soluble From 10 to 30

Sparingly soluble From 30 to 100

Slightly soluble From 100 to 1 000

000 to '10 000

Very slightly soluble From 1

Practically insoluble More than 10 000

Table -2: est

Specification Solvent Sample to be Solvent to add Result Remarks
taken about
Water

Acetone

Toluene
Does not
Practically insoluble 10 mg More than 100 ml Meets
Ethanol dissolve

Dilute acids

50 g/l sodium
hydroxide solution

Dissolve Copper tetrammine 50 mg 10 mL Completely leaving no

ammoniacal solution dissolve residue

[Copper Tetrammine, Ammoniacal Solution: Dissolve 34.5 g of copper sulfate in 100 mL of water and, whilst stirring, add
dropwise concentrated ammonia until the precipitate which forms dissolves completely. Keeping the temperature below 20",
add dropwise with continuous shaking 30 mL of strong sodium hydroxide solution. Filter through a sintered-glass filter (40)
(2.1.2), wash with water until the filtrate is clear and take up the precipitate with 200 mL of concentrated ammonia. Filter
through a sintered-glass filter (2.1.2) and repeat the filtration to reduce the residue to a minimum.l

Acceptance criteria: Practically insoluble in water, in acetone, in ethanol, in toluene, in dilute acids and in a 50 g/l solution of
sodium hydroxide.

Page 2 of 6
 VERITAS PHARMACEUTICALS LIMITED,
ffiritas Muradpur, Vannara, Mouchak, Gazipur, Bangladesh

STANDARD TEST PROCEDURE

Material Name: MICROCRYSTALLINE CELLULOSE (Avicel Ph 102) Bp/Ep

Doc. No.: TP/1 1 13005/01 Version:01 Prepared By: r-a*1v Approved ay,ffio1'\'
4c./avl1

3. ldentification

A. Place about 10 mg on a watch-glass and disperse in 2 ml of iodinated zinc chloride solution.

[Zinc Chloride Solution, lodinated: Dissolve 20 g of zinc chloride and 6,5 g of potassium iodide in 10.S mL of water. Add
0.5 g of iodine and shake for 15 minutes, filtering if necessary,l

Acceptance criteria: The substance becomes violefblue.

B. [Ph Eur 2.2.9]Transfer 1.300 g to a125 mL conicalflask. Add 25.0 mL of water R and 25.0 mL of cupriethylenediamine
hydroxide solution R. lmmediately purge the solution with nitrogen R, insert the stopper and shake
until completely
dissolved. Transfer an appropriate volume of the solution to a suitable capillary viscometer (2.2.g). fquilibrate
the
t
solution at25 0.1 'C for at least 5 min. Record the flow time (tr) in seconds between the 2 marks on the viscometer"
Calculate the kinematic viscosity (nr) of the solution using the following expression:

tr (kr)

where kr is the viscometer constant"

Dilute a suitable volume of cupriethylenediamine hydroxide solution R with an equal volume

of water R and measure the
flow time (tz) using a suitable capillary viscometer. Calculate the kinematic viscosity (nz) of the
solvent using the following
expression:

tz (kz)

where kz is the viscometer constant. \

Determine the relative viscosity (h,.) of the substance to be examined using the following expression:

vt lvt

Determine the inkinsic viscosity (hld by interpolation, using the intrinsic viscosity tabte (Table 0316.-1).

Calculate the degree of polymerisation (p) using the following expression:

95[nl.

M[(100 - byl00J

where m is the mass in grams of the substance to be examined and b is the loss
on drying as a percentage
Acceptance criteria: The degree of polymerisation is not more than 350.

pH [Ph Eur 2.2.3]

shake 5 g with 40 ml of carbon dioxide-free water for 20 min and cenkifuge

Acceptance criteria: 5.0 to 7.5 for the supernatant liquid.

Page 3 of 6
 VERITAS PHARMACEUTICALS LIMITED,
ffieritas Muradpur, Vannara, Mouchak, Gazipur, Bangladesh

STANDARD TEST PROCEDURE

MICROCRYSTALLINE CELLULOSE (Avicet ph 102) Bp/Ep

Doc. No.: TP/1 1 13005/01 Version: 01 Approved By]$1f,ol'l''l

Conductivity [Ph Eur 2.2,38]

Use as test solution the supernatant liquid obtained in the test for pH^ Measure
the conductivity of the supernatant liquid after a
stable reading has been obtained and measure the conductivity of the water used
to prepare the test solution.

Acceptance criteria: Not more than 75 pS.cm-1

Ether soluble substances

Place 10.0 g in a column about 20 mm in internal diameter and pass 50 ml of peroxide-free ether through the column.
Evaporate the eluate to dryness. Dry the residue at 1050 C for 30 minutes,
allow to cool in a desiccator and weigh. Carry out a
blank determination under the same conditions.

Calculation:
(Wz- Wr)x 100
Wr

Where, Wr= Weight of the a empty beaker determination in g

Wr = Weight of the column and the sample after drying in g
Wr = Weight of sample in g

Acceptance criteria: Maximum 0,05 % (5 mg) for the difference between

the weight of the residue and the weight obtained
from a blank determination.

7. Water soluble substances

Shake 5'0 g with 80 ml of water for 10 min. Filter with the aid of vacuum
into a tared flask. Eiaporate to dryness on a water-
bath Dry at 100-105 "C for t h, allow to cool in a desiccator and weigh. Carry out a biank determination under the same
conditions.

Calculation:
(Wz-Wr)x100
Ws

Where, Wr= Weight of the a empty beaker determination in g

Wr = Weight of the column and the sample after drying in g
Wr = Weight of sample in g

Acceptance criteria: Maximum 0.25 o/o

(12.5 mg) for the difference between the mass of
the residue and the mass obtained
from a blank determination.

Heavy metals [Ph Eur 2.2.8]

Test s-o^lution: Place the prescribed quantity (not more than 2 g)

of the substance to be examined in a silica crucible with 4 mL
of a 250 g/L solution of magnesium sulfate in dilute sulfuric ,iio_ts
svrrlrt. rvrx ,sing a flne glass rod. Fieat cautiously. lf the
mixture is liquid, evaporate gently to dryness on a water-bath. Piogressivety
neat to ignition and continue heating until an
almostwhite or at most greyish residue is obtalned. Carry outtt."ilnitrn
Jt a temperature not exceeding g00.c. Allow to
cool Moisten the residue with a few drops of dilute sulfuric acid
ts.svrvlvl. rvaporate, ignite again and allow to cool. The total
period of ignition must not exceed 2 h. Take up
the residue in 2 quantitiei, .r.j', or 5 mL, of dilute hydrochtoric acid (200/owtv).
Add 0'1 mL of phenolphthalein solution, then concentrated.ammonia
1rs srrrrf untira pinkcolour is ootaineo" cool, add glacial
acetic acid until the solution is decolorised and add 0.5 mL in
excesi. Filtei iinecessary and wash the fitter. Dilute to 20 mL
withwater.

Fage 4 of 6
 VERITAS PHARMACEUTICAI.S I.IMITED,
Muradpur, Vannara, Mouchak, Gazipur, Bangladesh
ffieritas
STANDARD TEST PROCEDURE
Material Name: MICROCRYSTALLINE CELLULOSE (Avicel Ph 102) BP/EP

Doc, No.: TP/1 1 13005/01 Version: 01 prepared BV: Naar.<V

4t/6t/t q
Approved By'$, il'tq

LeadStandardSolution(100ppmPb):lmmediately beforeuse,diluteleadstandardsolution(0"1 percentPb)tol0timesits

volume with water.

Lead Standard Solution (10 ppm Pb): lmmediately before use, dilute lead standard solution (100 ppm Fb)to 10 times its
volume with water.

Reference solution (standard): Prepare as described for the test solution, using the prescribed volume of lead standard
solution (10 ppmPb) instead of the substance to be examined. To 10 rnl of the solution obtained add 2 rnl of the test
solution.

Monitor solution: Prepare as described for the test solution, adding to the substance to be examined the volume of lead
standard solution (1 0 ppm Pb) R prescribed for preparation of the reference solution. To 1 0 mL of the solution obtained add 2
mL of the test solution.

Blank solution: A mixture of '10 mL of water R and 2 mL of the test solution.

To'l2mLofeachsolution,add2mLofbuffersolutionpH3.5R.Mixandaddtol.2 mLofthioacetamidereagentR.Mix
immediately. Examine the solutions after 2 min.

System suitability

the reference solution shows a slight brown colour compared to the blank solution,
-
- the monitor solution is at least as intense as the reference solution.
\
Result: Any brown colour in the test solution is not more intense than that in the reference solution.

lf the result is difficult to judge, filter the solutions through a suitable membrane filter (nominal pore size 0.45 pm). Carry out
the filtration slowly and uniformly, applying moderate and constant pressure to the piston. Compare the spots on the filters
obtained with the different solutions.

Acceptance criteria: Not more than 10 ppm

Loss on drying [Ph Eur 2.2.321

Dry a weighing bottle with stopper in an oven at 1050C for 30 minutes. Place it in desiccators, allow cooling and weighing with
stopper. Accurately weigh about '1.0 g of sample in the bottle and dry the stopper bottle in an oven at 100-1050 0"Remove the
bottle from oven, stopper it, and allow cooling in desiccators and reweigh. Calculate the percentage of loss on drying using the
following formula:

Calculation:
(W1-W2)x100

. (w1_c)

Where, C = Weight of the weighing bottle (in g)

W1 = Weight of the weighing bottle and sample before drying (in g).
W2 = Weight of the weighing bottle and the sample after drying (in g).

Acceptance criteria: Not more than 7 0%

Page 5 of 6
 VERITAS PHARMACEUTICAI.S LIMITED,
ffiritas Muradpur, Vannara, Mouchak, Gazipur, Bangladesh

STANDARD TEST PROCEDURE

Material Name: MICROCRYSTALLINE CELLULOSE (Avicel Ph 102) BP/EP

Doc. No.: TP/1 1 13005/01 Version: 01 Prepared By; lf;J1.,. Approved By: Szq$l, l'Y

10. Sulphated ash [Ph Eur 2.2.32]

Heat a platinum dish to redness for 1 0 minutes, allow to cool in a desiccator and weigh" Flace 1 g of the sample
in the dish, moisten with sulphuric acid, ignite gently, again moisten with sulphuric acid and ignite at about 800".
Cool, weigh again, ignite for 15 minutes and repeat this procedure until two successive weighings do not differ by
more than 0.5 mg.

Calculation : (Wr-Wr)X100
(Wz -Wr)

= % of residue on ignition

Where,
Wr = weight (g) of empty crucible
Wz = weight (g) of crucible along with sample before ignition.
Wr= weight (g) of crucible along with sample after ignition.

Acceptance criteria: Not more than 0.1%

11" Microbialcontamination [Ph Eur 2.6.12 &2.6.13]

As per microbiological SOP : VPL-MB-016-00

Acceptance criteria:

TAMC: Not more than 103 CFU/g

TYMC: Not more than 10' CFU/g
Absence ol Escherichia coli
Absence of Pseudomonas aeruginosa
Absence of Staphylococcus aureus
Absence of Salmonella

12. Revision History

Document No. Version No Date Reason

vRME/M/07121005 00 Jan2A12 Initial Documents for MICROCRYSTALLTNE CELLULOSE 1028p

TP/1'1 13005/01 01 02Feb2014 To detail the procedure for analysis of MICROCRySTALLINE

CELLULOSE (Avicel Ph 102) BP/EP

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