QC of Packaging Material

QC of Packaging Material

CONTENTS

INTRODUCTION

PARAMETERS FOR TESTING

CLASSIFICATION OF TESTS

TESTS FOR GLASS

TESTS FOR PLASTICS

TESTS    FOR RUBBERS

TESTS FOR METALS

TESTS    FOR PAPER AND BOARDS

INRTODUCTION-

Selection of materials for manufacture of packages is governed by chemical and physical properties of material and product.

Quality control of these materials is very important aspect for packaging process, various tests are employed to determine the quality of theses packaging materials.

Quality control forms the backbone of pharmaceutical industry. Quality control starts at design stage.

TYPES OF PACKAGING MATERIALS USED

METALS

GLASS

PLASTIC

PAPER AND CARD- BOARD

RUBBER

PARAMETERS FOR TESTING

IDENTITY Critical identifaction, inspection and analysis certified from suppliers

LIGHT TRANSMISSION In case of strips and somelight sensitive substances, light transmission limits have to assured. It should not be more than 10% of limit in case of light sensitive conpounds

EXTRACTABLES to assure that contents of material do not leach out. It is very important in case of inhalation, injectables and implant products

PERMEATION There are two ways of permeation check: For solid dosage form it is measured as moisture moving into container. For liquids it is measured as water migrating from product to container

CLASSIFICATION OF TESTS

Chemical

The pH value of materials, chloride and sulphate in paper or board, alkalinity of glass, compatibility test with chemicals or medicament are typical of chemical tests

Mechanical

Standard tests are available for effect of creasing, folding and so on

Environmental  

Materials may be tested by standard methods of absorption of water, permeability to water vapours, gases, oils, odours etc and for characteristics such as light transmission

QUALITY CONTROL TESTING OF GLASS

Glass is one of most widely used materials for parenteral products, each glass container must be to be tested by following manner.

Pharmacopoeial tests:

Test for surface hydrolytic resistance

Test for hydrolytic resistance of powdered glass

Light transmission test for coloured glass

Test for resistance to thermal shock

Surface hydrolytic resistance test

Powder glass hydrolytic resistance test

Principle

Amount of alkali leached from glass is determined in this test. The container is filled with pure water and maintained at specified autoclaving condition for specified time period. The leached alkalis titrated against the acid at neutralization point it will give the amount of alkali leached.

Nominal capacity of container (ml)

number of containers to be used

Volume of test solution to be used for titration (ml)

Up to 3

20

25

5 or less

10

50

6 to 30

5

50

More than 30               

3    

100

Procedure

Wash with CO2 free water

Fill it with CO2 free water (up to maximum volume) Autoclave (120 degree C for 60 min)

Take sample of water and titrate against 0.01N HCL (Blank reading)

Amount of acid required must meet the specification of IP

POWDERED GLASS TEST

Hammer the container and collect 100g glass (fragments should not be greater than 25mm)

Powder it to obtain 20g fragment on retain on 250 micron sieve but pass through 425 micron sieve (as per IP )

Magnet passing to purify

Now perform as per previous test by adding 100ml CO2 free water and match the result with IP specifications

LIGHT TRANSMISSION TEST FOR COLOURED GLASS

Break the glass with carborundum or diamond wheel

Select wall section

Put in specimen holder of spectrometer with care place test specimen in the spectrometer with its cylindrical axis parallel

To the slit and in such a way light beam is perpendicular to the section

Measure the transmission of specimen with reference to air in spectral region of 290-240 nm

TEST FOR THERMAL SHOCK RESISTANCE

Particularly used for blood products or biological products

Empty container in autoclave (140◦ C for 30min)

Place in oven (2500C for 1 hour)

Fill 70% container with 0.9% NaCl and cool to - 20 degrees C for 1 hr

After restoring to room temperature the container must comply with test for resistance to centrifugation.

TEST FOR ARSENIC

Carry out test on ampoules, inner and outer surfaces are washed five times with distilled water

Prepare a test solution as described for adequate ampoules to 50ml

Pipette 10ml of test solution from combined contents of all ampoules into flask

Add 10ml of nitric acid and evaporate to dryness on water bath

Dry the residue in an oven at 1300C for 30 min

Cool, add to the residue to 10 ml of hydrazine molybdate reagent

Heat under reflux on water bath for 20 min

Cool to room temperature. Determine absorbance of resulting solution at 840 nm using 10.0 ml of hydrazine molybdate reagent as blank

The absorbance of test should not exceed that obtained by 0.1ml of arsenic standard solution.

TESTS ON PLASTIC MATE

PHYSICO-CHEMICAL TESTS:-

The following tests are based on the extraction of the plastic material, and it is essential that the designated amount of the plastic be used. Also, the specified surface area must be available for extraction at the required temperature.

1.     Appearance

2.     Light absorption

3.     pH

4.     Non-volatile matter

5.     Residue on ignition

6.     Heavy metals

7.     Buffering capacity

8.     Oxidisable substances

TESTS FOR PLASTIC CONTAINERS

Tests comply for non-parenteral preparations

1. Leakage test: Fill ten container with water. Fit with intended closures and keep tem inverted at room temperature for 24 hour. There are no signs of leakage from any container.

2. Collapsibility Test: This test applicable to containers. Which are to be squeezed in order to remove the contents. A container by collapsing inwards during use yields at least 90% of its nominal contents at the required rate of flow at ambient temperature.

Solution S.

Fill a container to its nominal capacity with water and close it. If possible using the usual means of closer: otherwise close using a sheet of pure aluminium. Heat in an autoclave so that a temperature of 121 + 20 is reached within 20to 30 minutes and maintained at this temperature for 30min. if heating at 1210 leads to deterioration of the container, heat at 1000 for 2 hours.

Using 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 themeprature and for the time used for the preparation of solution S.

Clarity and color of solution S

Solution s is clear and it’s colorless

Acidity and alkalinity

To a volume of solution S corresponding to 4% of the nominal capacity of the container add 0.1ml of Phenolphthalein solution. The solution is colorless. Add 0.4ml of 0.1M sodium hydroxide, the solution is pink. Add 0.8ml od 0.01M HCl and 0.1ml of methyl red solution, the solution is orange-red or red.

Light absorption

The light absorption in the range 230nm to 360nm of solution S using a blank prepared as described under solution S is not more than 0.20

Reducing Substance

To 20.0ml of solution of S add 1 ml of dilute Sulphuric acid and 20.0ml of 0.002M potassium permanganate. Boil for 3 min, cool immediately, add 1gm of potassium iodide and titrate with 0.01M sodium thiosulphate, using 0.25ml of starch solution as indicator, carry out a titration using 20.0ml of blank prepared as described under solution S, the difference between the titration volume is not more than 1.5ml.

Transparency

Fill the container previously used for the preparation of solution S to its nominal capacity with a 1 in 200 dilution of the standard suspension for a container made from polyethylene or polypropylene. For container of other material use a 1 in 400 dilution, the cloudiness of the suspension is perceptible when viewed through the container and compared with a similar container filed with water.

3. Clarity of aqueous extract: Select unlabelled, unmarked and non- laminated portions from suitable containers, taken at random sufficient to yield a total area of sample required taking into account the surface area of both sides Cut these portions into strips none of which has a total area of more than 20 cm2. Wash the strips free from extraneous matter by shaking them with at least two separate portions of distilled water for about 30 seconds in each case, then draining off the water thoroughly.

4. Transparency test: Fill five empty containers to their nominal capacity with diluted. Suspension as described in IP 1966. The cloudiness of the diluted suspension in each container is detectable when viewed through the containers as compared with a container of the same type filled with water.

FOR PARENTERALS

Water Vapour permeability test: Fill five containers with nominal volume of water and heat seal the bottles with an aluminum foil- poly ethylene laminate or other suitable seal. Weigh accurately each container and allow to stand (without any overwrap) for 14 days at a relative humidity of 60+5% and a temperature between 20 and 25 0C Reweigh the containers. The loss in weight in each container is not more than 0.2%.

NON VOLATILE RESIDUE TEST

Fill five containers with dilute suspension. The cloudiness of diluted suspension in each container is detectable when viewed through container is detectable when viewed through containers as compared with a container of same type filled with water. Evaporate 100 ml extract. Allow it to dry at 105 C. residue weighs not more than 12.5mg.

RESIDUE ON IGNITION - This test is performed when NVR is greater than 5 mg

HEAVY METALS - This test detects the presence of metals like lead, tin, zinc etc

BUFFERING CAPACITY - This test measures the acidity or alkalinity of the extract

BIOLOGICAL TESTS: -

The USP has provided its procedures for evaluating the toxicity of plastic materials Essentially the tests consist of three phases:

Implantation test: Implanting small pieces of plastic material intramuscularly in rabbits.

Systemic injection test: Injecting eluates using sodium chloride injection, with and without alcohol intravenously in mice and injecting eluates using poly ethylene glycol 400 and sesame oil intraperitoneally in mice.

Intracutaneous test: Injecting all four eluates subcutaneously in rabbits. The reaction from test samples must not be significantly greater than nonreactive control samples

TESTING FOR OPHTHALM

PLASTIC CONTAINERS FOR OPHTHALMIC PREPARATIONS:- Plastic containers for ophthalmic preparations comply with the following tests:

1 Leakage test; Collapsibility test Clarity of aqueous extract; Non- volatile residue Comply with the tests described under Plastic containers for Non- parenteral Preparations.

2 Systemic injection test; Intracutaneous test Comply with the tests described under Plastic containers     for Parenteral Preparations.

3 Eye irritation test. This test is designed to evaluate responses to the instillation of extracts of material under examination in the eye of a rabbit.

QUALITY CONTROL TESTING FOR CLOSURES

The closure is normally the most vulnerable and critical component of a container as far as stability and compatibility with the product is concerned.

Suitable closing of the container is necessary because

1. It prevents loss of material by spilling or volatilization.

2. It prevents the deterioration of product from the effects of environment such as moisture, oxygen, or carbon dioxide.

3. It avoids contamination of the product from dirt, microorganism or insects

QUALITY CONTROL FOR RUBBER CLOSURES

Rubber closures are used to seal the cartridges, vials and bottles, providing a material soft and elastic enough to permit entry and withdrawal of a hypodermic needle without loss of integrity of sealed containers.

FRAGMENTATION TESTS

This test is applicable to closure intended to be pierced by needle and closures used for aqueous preparations

SELF SEALABILITY TEST

This test is applicable to closures intended for multidose containers

SAMPLE PREPARATION

Wash the closures by agitation in 0.2% w/v solution of anionic surfactant for 5 minutes and then rinse 5 times with water.

Place number of washed closures (contain 100 cm² surface area) in suitable borosilicate glass.

Add 200 ml of water per 100cm² surface area of closures and weigh it

Now cover the mouth of container with aluminum foil and heat in autoclave and maintain temperature of 119-1230C for 30 minutes

Cool at room temperature for 30 min and make up the original weight with water

Shake and immediately separate the solution from closures by decantation

Dry the treated closure 640C, at pressure not more than 0.7 Kpa for 24 hours

1) STERILITY TEST

When treated closures are subjected to sterilization test at 64 -660C and pressure of about 0.7 Kpa for24 hours.

2) RESIDUE ON EAPORATION

50ml of solution A is evaporated to dryness at 1050C. Then weigh the residue NMT 4mg

3) FRAGMENTATION TEST

1. For closures for aqueous place a volume of water corresponding to the nominal volume mines 4ml in each of 12 clean vials

2. Close the vials with ‘prepared ‘closures to allow to stand for 16 hours

3. For closures for dry preparations close 12 clean vials with prepared closures

4. Using hypodermic needle with an external diameter of 0.8 mm inject 1ml of water into the vial and remove 1ml of air

5. Carry out this operation 4 times with new needle each time. Pass the liquid into the vials through a filter with pore size of 0.5 micrometer

6. Number of fragments is NMT 10 except in case of butyl rubber

4) SELF SEALABILITY TEST

This test is applicable to closures intended to use with water close the vials with the prepared closures

For each closure, use a new hypodermic needle with an external diameter of 0.8mm and pierce the closure 10 times, each time at a different site

Immerse the vials upright in a 0.1% w/ solution of methylene blue and reduce the external pressure by 27Kpa for 10 minutes

Restore the atmospheric pressure and leave the vials immersed for 30 minutes. Rinse the outside of the vials. None of the vials contains any trace of colored solution

5) PH OF THE AQUEOUS EXTRACT

20ml of solution A is added with 0.1ml bromothymol blue when it is added with a small amount of 0.01ml NaOH which changes the color from blue to yellow. The volume of NaOH required is NMT 0.3ml and if it is done with HCl, the volume of HCl needed should not be more than0.8ml

6) LIGHT ABSORPTION TEST

It must be done within 4 hours of preparing solution A. it is filtered through 0.5 micron filter and its absorbance is measured at 220nm to 360nm. Blank is done without closures and absorbance is NMT 2.0

7) REDUCING SUBSTANCES

20ml of solution A is added with 1ml of 1M H2SO4 and 20ml of 0.002M KMnO4 and boil for 3minutes then cool and add 1gm of potassium iodide which is titrated with sodium thiosulphate using starch as an indicator . Blank is done and difference between the titration volumes is NMT 0.7ml.

8) RESIDUE ON EVAPORATION

50ml of solution A is evaporated to dryness at 105. Then weigh the residue NMT 4mg

QUALITY CONTROL FOR METAL

TINS

DESCRIPTION

Metallic tins having smooth inner surface.the upper surface sealed consists a clip to break the seal. The lower surface is open

DIMENSIONS

Height – measure the height of in mm of 10 metallic tin, individually from the lower surface edge to upper rim.

DIAMETER

Inner diameter – measure the inner diameter of 10 metallic tins. Limit NLT 98mm

Outer diameter – limit NLT 105mm

CLEANLINESS CHECK

Should not be damaged, stained or consist of foreign part.

QUALITY CONTROL FOR STRIPS AND BLISTERS

PROCEDURE

3/4th of water is poured in desiccators. The strips and blisters were place inside desiccators and vacuum is applied.

Vacuum was then released and strips, blisters were taken out. The water present over the outer surface of the packages was wiped off with tissue paper

The contents of strips and blister packages were removed and presence of moisture was checked. If there is no leakage, the contents will not be wetted

This indicates perfect sealing of the packages

QUALITY CONTROL OF PAPER AND BOARD

The test pieces of paper and board are prepared under standard conditions such as

Temperature: 23± 1, Relative humidity: 50%± 2%

Moisture Content- Substance will be measured at temperature specified for the test

Folding endurance- Fold the test piece back and forth until rupture occurs

Air permeability- Important for using light weight uncoated paper on machine having vacuum pick up system

Tensile strength- Maximum tensile force per unit width that a paper will withstand before breaking

Stiffness- Degree of resistance offered by paper

TESTING FOR PHARMACEUTICAL COILS

Table 35-4.  Comparison of Pharmaceutical Coils

Test

Cotton

Rayon

Polyester

Residual  Hydrogen Percxlce Concentration                             

NMT 50 ppm  is found  using either method

 

Not applicable for rayon

 

Not applicable for synthetic coil

 

Loss on Drying <731>              

Dry 5.00 g of fibers  In an oven at 105° to constant weight: It loses NMT 8.0% of Its weight

 

Dry 5.00 g of fibers  in an oven at 105° to constant weight: It loses NMT 11.0% of its weight

 

Dry 5.00 g of fibers in an oven at 105° to constant weight:  It loses NMT 0.5% of lts wetght

 

Residue on Ignition <281>      

NMT 0.20% on a 5.0 g sample

 

NMT 1.50% on a 5.0 g sample

 

NMT 0.5% on a 5.0 g sample

 

Water-Soluble Substances     

The  residue weighs NMT 0.35%

 

The  residue weighs NMT 1.0%

 

Not applicable for synthetic coil

 

Fatty Matter                              

The weight of the residue of a 10.00 g sample does not exceed 0.7%

 

The  weight of residue of a 5.00 g sample does not exceed 0.5%

 

Not applicable for synthetic coil

 

Possible additives of chemicals  which could react

 

Bleach and  dyes

Furfural

 

Antistatic Agents

 

PACKAGING MATERIAL SPECIFICATIONS:

Printed strip rolls:

Common name, Code number, Description, Color plan and outline, Quality of printed matter, Seal quality, Effect of warmth, Name of endorsed supplier, Frequency of re- investigation of put away material, Precaution, and Date of issue of determination

Containers:

name of the medication and quality, Code number, Description, Dimensions (length, width, stature), Color plan, Quality of printed matter, Printed matter, Gram per square meter, Suitability, Name of affirmed supplier, Frequency of re-assessment of put away material, and Date of issue of specification

Bottles:

Common name, Code number, Description, Total tallness, Neck tallness, Body distance across, Type of glass, Overflow limit, Suitability, Name of affirmed supplier, and Date of issue of particular

CONCLUSION

•THE TESTING OF PACKAGING MATERIALS IS ALMOST REQUIRED FOR ANY PHARMACEUTICAL INDUSTRY.

•THE MATERIAL OF A PACKAGE AFFECTS QUALITY, STABILITY AND EFFICACY OF DRUG PRODUCT.

•THE COST OF MATERIAL OF A PACKAGE SHOULD BE AS LOW AS POSSIBLE WITHOUT COMPROMISING THE QUALITY OF PRODUCT

•IT SHOULD PASS THE SPECIFICATIONS OF TESTS BEFORE IT REACHES THE MARKET.

•THE TYPE OF TESTS FOLLOWED SHOULD BE ACCORDING TO REQUIREMENTS OF REGULATORY AGENCIES.

 

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