lesson - 40 packaging materials science- iii qc tests of

Lesson - 40

Packaging Materials Science- III

QC tests of packaging materials

-Dr Ajay Semalty

Department of Pharmaceutical Sciences,

H.N.B Garhwal University (A Central University)

Srinagar Garhwal-246174

Learning outcomes

After learning this module you will be able to understand

• The standard methods of ascertaining quality of packaging material

and containers

Lesson Plan

QC tests for packaging materials

• Glass

• Plastic

• Metal

• Closures

QC Test for Glass

• Hydrolytic Resistance

• Powdered glass test.

• Water attack test.

• Arsenic limit test.

• Light transmission test

Hydrolytic resistance (IP)

Module 40 Packaging Materials Science III

MOOC: Industrial Pharmacy-I by Dr Ajay Semalty (Course Coordinator), HNB Garhwal

University (A Central University) Srinagar (Garhwal) Uttarakhand, India 2

• The test is done to determine whether the alkali leached form the

surface of a container is within the specified limits or not.

• The amount of acid that is necessary to neutralize the released alkali

from the surface is estimated

• The leaching of alkali is accelerated using elevated temperature for a

specified time

• End point indicator: Methyl red (acid-base titration).

Choosing container numbers/ volume

Capacity of

container

(mL)

No. of container

used

Volume of test solution to

be used for titration (ml)

upto 3 20 25

5 or less 10 50

6 - 30 5 50

More than 30 3 100

Test 1 -Surface glass test

Rinse containers twice with water

Wash containers Fill the containers

with fresh DW (90%) Cover with aluminum

foil

Autoclave at 100º-120ºC for 20 min

Maintain at 120ºC for 1 hr

At lower temp for 40 min

Remove containers & cool

Titrate it within 1 hour with the

specified volume of test solution

Titrate with 0.01 M HCl (end point

colourless)

The result is not greater than the

value stated in next Table




Test 2

• Rinse container twice with water and with 4%volume solution of HF

• Allow to stand for 10min

• Empty the container

• Rinse 5 times with water

• Carry out test similar test 1




Powdered Glass Test (PGT)

The PGT is performed to estimate the amount of alkali leached from the

powdered glass at the elevated temperatures. Leaching is assessed by acid

base titration with 0.02N sulphuric acid using methyl red as an indicator.

• Step-1: Preparation of glass specimen:

• Step-2:Washing the specimen:

Step-1: Preparation of glass specimen:

Few containers are rinsed thoroughly with purified water and dried with

stream of clean air. Grind the containers in a mortar to a fine powder and pass

through sieve no. 20 and 50.

Step-2: Washing the specimen:

10gm of the above specimen is taken into 250 ml conical flask and wash it

with 30 ml acetone. Repeat the washing, decant the acetone and dried after

which it is used within 48hr.

Procedure (Brief)

• 10gm sample is added with 50ml of high purity water in a 250ml flask.

• Place it in an autoclave at 121⁰ C±2⁰ C for 30min.Cool it under running

water.

• Decant the solution into another flask, wash again with 15ml high purity

water and again decant.

• Titrate immediately with 0.02N sulphuric acid using methyl red as an

indicator and record the volume.

Fig. 1. Detail Procedure PGT (USP)

• Transfer 10g of prepared specimen in 250mL conical flask

• It should be digested previously with high purity water in bath at 90°C

• Add to conical flask containing 50ml of high purity water




• Cap all the flask

• Autoclave (continue heating for 10min)

• Close vent cock

• Adjust temp to 121°C

• Hold the temp (121°C±221°C for 30min)

• Reduce the heat & wait for autoclave to cool

• Cool the flask in running water

• Decant water

• Wash the residual glass (4 times with 15ml high purity water)

• Add the decanted washing to main portion

• Add 5 drops of methyl red solution

• Titrate immediately with 0.02N Sulphuric Acid

• Record the volume of 0.02N Sulphuric Acid

• Volume doesn’t exceed the limit

USP acceptance criteria PGT

Type of CONTAINER Volume of 0.02N sulphuric

acid (mL)

Type I 1.0

Type II 8.5

Type III 15.0




Water Attack test (USP)

The test is done only for treated soda lime glass containers under the

controlled humidity conditions which neutralize the surface alkali and glass

become chemically more resistant

Principle: to detect the leached alkali from the surface of the container.

Brief Procedure: WAT

• Rinse thoroughly with high purity water.

• Fill each container to 90% of its overflow capacity with water

• autoclaved at 121⁰ C for 60min then it is cooled and the liquid is

decanted which is titrated with 0.02N sulphuric acid using methyl red

as an indicator.

• The volume of sulfuric acid consumed is the measure of the amount of

alkaline oxides present in the glass containers.

Detail Procedure:

• Rinse 3 or more containers with high purity water

• Fill each container to 90% of its overflow capacity

• Cap all the flasks, autoclave for 60min

• Empty the contents & cool the contents in 250ml conical flask to a

volume of 100ml

• Add five drops of methyl red solution

• Titrate with 0.02N Sulphuric Acid

• Record the volume consumed

• Volume should not exceed limits

USP acceptance criteria WAT




Type of CONTAINER Volume of 0.02N sulphuric acid

(mL)

Type II (100 mL or below) 0.7

Type II (About 100 mL) 0.2

Arsenic limit test

• Inner & outer surfaces are washed 5 times with freshly prepared

distilled water

• Prepare 50ml using adequate number of test solution

• Pipette out 10 ml of test solution from combined content of

ampoule into flask

• Add 10ml of HNO3

• Evaporate the dryness on water bath

• Add the residue in an oven at 130°c for 30min

• Cool, add to hydrazine molybdate reagent to dissolve

• Heat under reflux on water bath for 20 min

• Cool to room temperature

• Determine the absorbance of reducing solution at 840nm using

hydrazine molybdate reagent as a blank




Light Transmission Test

Maximum % light transmission at any wavelength between 290-450nm.

Information provided to patient may include:

• Identification no. for dispensing records.

• Name, strength & quantity

• Storage instructions.

• Direction for use.

• Name and address of dispensers.

Thermal Shock Test

• Place the samples in upright position in a tray. Immerse the tray into a

hot water for a given time and transfers to cold water bath, temp of

both are closely controlled.

• Examine cracks or breaks before and after the test. The amount of

thermal shock a bottle can withstand depends on its size and design.

Small bottles withstand a temp differential of 60 to 80⁰ C and large

bottle 30 to 40 ⁰ C.

• A typical test uses 45 ⁰ C temp difference between hot and cold

water.

Leakage Test

• Fill 10 containers with water, fit with intended closures and keep them

inverted at room temperature for 24hr.

• The test is said to be passed if there is no signs of leakage from any

container.

Internal Bursting Pressure Test

• instrument used is American glass research increment pressure tester

• The test bottle is filled with water and placed inside the test chamber.

• A scaling head is applied and the internal pressure automatically

raised by a series of increments each of which is held for a set of time.

• The bottle can be checked to a preselected pressure level and the test

continues until the container finally bursts.




QC test for Plastic Containers

A. Noninjectable preparations

• Collapsibility test

• Clarity of aqueous extract

• Non-volatile residue

B. Injectable preparations

• Collapsibility test

• Leakage (as in glass test)

• Clarity and colour of solution

• Acidity or alkalinity

• Reducing substances

• Light absorption

• Water vapor permeability

• Transparency

Collapsibility test

Applicable to containers which are to be squeezed in order to remove

contents. Yield: 90%of its contents at required rate of flow at ambient temp.

Clarity of aqueous extract

Clarity of aqueous extract Select unlabelled portion from a suitable

containers Cut these portions into strips Wash it with extraneous matter by

shaking with two separate portions of distilled water Transfer to flask –

previously washed with chromic acid Rinse with distilled water add 250ml

d.w. Cover the flask autoclave at 121 0Ċ, 30min Colourless , free from

turbidity

Clarity and colour of solution




• Solution S is clear and is colorless.

Solution S

• Fill a container to its nominal capacity with water and close it, if

possible using the usual means of closure; otherwise close using a

sheet of pure aluminium. Heat in an autoclave so that a temperature of

121 ± 2º is reached within 20 to 30 minutes and maintain at this

temperature for 30 minutes.

• If heating at 121º leads to deterioration of the container, heat at 100º

for 2 hours. (Use solution S within 4 hours of preparation)

Blank.

Prepare a blank by heating water in a borosilicate glass flask closed by a sheet

of pure aluminum at the temperature and for the time used for the preparation

of solution S.

Acidity or alkalinity

• To a volume of solution S corresponding to 4 per cent of the

nominal capacity of the container add 0.1 ml of phenolphthalein

solution.

• The solution is colorless. Add 0.4 ml of 0.01M sodium hydroxide.

• The solution is pink.

• Add 0.8 ml of 0.01M hydrochloric acid and 0.1 ml of methyl red

solution.

• The solution is orange-red or red.

Reducing substances

• To 20.0 ml of solution S add 1 ml of dilute sulphuric acid and 20.0 ml

of

• 0.002M potassium permanganate. Boil for 3 minutes. Cool

immediately.

• Add 1 g of potassium iodide and titrate immediately with 0.01M

sodium thiosulphate, using 0.25 ml of starch solution as indicator.




• Carry out a titration using 20.0 ml of the blank prepared as described

under Solution S. The difference between the titration volumes is not

more than 1.5 ml

Light absorption

• The light absorption in the range 230 nm to 360 nm of solution S

using a blank prepared as described under Solution S is not more than

0.20.

Water Vapor Permeability

• Fill 5 containers with nominal volume of water and heat seal the

bottles with aluminium foil.

• Weigh accurately each container and allow to stand for 14 days at

humidity- 60 ± 5% temp. 20 ºĊ and 25ºĊ.

• Reweigh the containers.

• Loss in wt in each container is NMT 0.2%

Transparency test

• Standard suspension preparation: 1gm hydrazine sulphate in 100ml

water and set aside for 6hr.

• Take 25ml of this solution and add 25ml of 10%w/v hexamine and

stand for 24hr.

• Test solution preparation: Sample is prepared by 16fold dilution of

the standard suspension.

• Fill 5 containers cloudiness detectable when compared to water filled

containers.

• Absorbance is measured at 640nm and the range is within 0.37 and

0.43.




QUALITY CONTROL OF CLOSURES

• Sterility

• Fragmentation

• Self sealability

• pH of aqueous extract

• Light absorption test

• Reducing substances

• Residue on evaporation

QC: Closure

PREPARATION OF SAMPLE(SOL.-A): Wash closures in 0.2%w/v of anionic

surface active agents for 5min. Rinse 5 times with dist water and add 200ml

water and is subjected to autoclave at 119 to 123:C for 20 to 30min covering

with aluminum foil. Cool and separate solution from closure (soln-A).

• Step 1 Wash closure in 0.2% w/v of anionic surfactant for 5 min

• Step 2 Rinse 5 times with distilled water and add 200ml

• Step 3 Further subjected to autoclave and covering with

aluminum foil

• Step 4 Allow to cool and separate solution from closure

2. Fragmentation test

• Take 12 clean vials and place closures containing 4ml of water

• Allow to stand for 16 hrs.

• Use hypodennic needle to inject 1m1 of water into the vial & remove

1 m1 of air

• Pass the water present in vial through a filter with pore size of 0.5pm

• Carry this operation for 4 times with new needle each time




• No. of fragments of closure retain should be as per the limits

Limit:

No. of fragments – Not More than 10 (in case of butyl rubber)

No. of fragments – Not More than 15

3. Self – sealability

The test is Applicable to closures intended to be used with water.

4. pH of aqueous extract

• Take 20ml of sample solution

• Add 0.1ml of bromothymol blue

• Add 0.01M of NaOH till color change from Blue to Yellow.

• Volume required is measured

Limits:

• Vol. of NaOH — NMT 0.3 ml

Vol. of HCl—NMT 0.8 mL




Light Absorption Test

The test must be done within 4hrs of preparing solution A. It is filtered

through 0.5μ filter and Its absorbance is measured at 220 to 360nm. Blank is

done without closures and absorbance is NMT 2.0.

Reducing substances

• 20ml of solution A is added with 1ml of 1M H2SO4 and 20ml of 0.002M

KMnO4 and boil for 3min

• Cool and add 1gm of potassium iodide which is titrated with sodium thio-

sulphate using starch as an indicator.

• Blank titrationi is done and the difference between titration volumes is

NMT 0.7ml.

Residue on Evaporation

50ml of solution A is evaporated to dryness at 105 degree C. Weigh the

residue. Limit: NMT 4mg.

Penetrability

• To measure the force required to make a hypodermic needle penetrate

easily through closure.

• measured by using piercing machine.

• The piercing force must not exceed a stated value, the hypodermic

needle can get damage as a result of undesirable hardness of closure.

QC test for metallic container

Step 1

Take 50 empty tubes filled with ointment base, sealed & kept overnight

Step 2




A metal bacteriological filter assembly fitted with filter paper & heated to

melting range of ointment base

Step 3

Base from all tubes squeezed at certain rate & passed through filter under

vacuum. Then wash with CHCl3 and observed for particles

Acceptance criteria

Particles 1 mm and above 50

Particles 0.5 mm to 1 mm 10

Particles 0.2 mm to 0.5 mm 02

Particles less than 0.2mm Nil

Total score 62

Acceptance Limit

Total Score Test result/ remark

< 100 Lot of tube passes test

> 150 Lot of tubes fails

100 – 150 test is repeated again with 50

more tubes

QUALITY CONTROL OF STRIP AND BLISTERS

• 3/4th of water is poured in desiccator

• Strip and Blister are placed inside desiccators

• Apply vacuum

• Strips & blisters are taken out

• Wipe the water present at surface




• The content is removed

• Presence of moisture is checked

• If content is not wet, no leakage is there

• It indicates perfect sealing

Take Away Message

• To ensure safety, stability and efficacy packaging QC tests are

performed.

• HRT, PGT, WAT, transparency glass test

• For plastic, collapsible tubes, metallic tin, rubber closures

Further Readings

• USP/ IP

• Banker GS, Rhodes CT, Modern Pharmaceutics, CRC Press.

• Aulton ME (ED), Pharmaceutics: The science of Dosage form design,

II edn, Churchill Livingstone, London, 2002.

• Dean. Evans, Hall, Pharmaceutical Packaging technology, Taylor &

Francis, London.

References/ Credits

• USP/ IP

• Ansel’s Pharmaceutical Dosage Forms and Drug Delivery Systems.

Philadelphia: Lipincott Williams and Wilkins.

• Augsburger LL, Hoag SW (Eds), Pharmaceutical Dosage Forms:

Tablets, Volume 1, III Edn, Informa healthcare, 2008

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