QUALITY CONROL TEST FOR PLASTIC CONTAINERS

FACILITATOR Dr.VISHAL KUMAR GUPTA .N ASST.PROFESSOR DEPARTMENT OF PHARMACEUTICS J.S.S. COLLEGE OF PHARMACY MYSORE.
PRESENTED BY VENKATA SAIRAM .K M.PHARM I YEAR PHARMACEUTICAL ANALYSIS

Contents
Introduction to Containers

Introduction to Plastic containers

Classification of plastic Types of Plastic containers uses in

Pharmaceuticals General Requirements Tests on Containers Tests on Containers material Tests on Extracts
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INTRODUCTION TO CONTAINERS:
Container - Closure system components are also termed packaging components & are grouped into two categories:

1. Primary Packaging Components: direct contact with the dosage form

Containers (e.g., ampules, vials, and bottles), Container liners, Closure liners Closures (e.g., screw caps, stoppers etc)

2. Secondary Packaging Components: which are not or will not be in direct contact with the dosage form.
Container labels, Administration accessories, Shipping containers, etc.
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INTRODUCTION TO PLASTIC CONTAINERS:

Plastic containers for pharmaceutical products are made from

following plastics based on the Polymers :

Polyethylene Polypropylene Polyvinyl chloride Polystyrene Polyethylene terephthalate
Containers consist of one or more polymers together with certain

additives if necessary.
Additives may consist of Antioxidants, Lubricants, Plasticisers

and impact modifiers but not antistatic agents and mould-release agents.
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 Container should be made of materials that do not leach out any ingredient into contents in such quantities so as to alter the efficacy or stability of the product or to present a toxic hazard. Plastic container chosen for any particular product should be such that the ingredients of the product in contact are not significantly adsorbed on its surface and do not significantly migrate into or through the plastic.

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CLASSIFICATION OF PLASTIC:
There are two types of plastics:

Thermoplastics Polymer Thermosetting Polymer

Thermoplastics are the plastics that don't undergo chemical

change in their composition when heated and can be molded again and again
Thermosets can melt and take shape once; after they have

solidified, they stay solid.

The raw materials needed to make most plastics come from

petroleum and natural gas

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TYPES OF PLASTICS :
Thermosets Urea formaldehyde (UF) Phenol formaldehyde Melamine formaldehyde (MF) Epoxy resins (epoxides) Thermoplastics Polyethylene{HDPE LDPE} Polyvinylchloride(PVC)

Polystyrene Polypropylene Nylon(PA) Polyethylene terepthalate(PET) Polyvinylidene chloride(PVdC)

Polyurethanes (PURs) Polyesters

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Polycarbonate Acrylonitrile 13 February 2013 butadiene styrene(ABS)

Advantages:
Choice of material and grade Processes of fabrication and decoration

Wide selection in design and physical and chemical properties

Economical

Disadvantages:
Possible extraction, interaction, adsorption, absorption, lightness and hence poor physical stability.
All are permeable to some degree to moisture, oxygen, carbon dioxide etc and most exhibit electrostatic attraction, allow penetration of light rays. Stress cracking- (because of wetting agents, detergents and some volatile oils)
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QC & QA Panelling or cavitation swelling or dimpling

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TYPES OF PLASTIC CONTAINERS USES IN PHARMACEUTICALS:

Plastic Containers for Injectable Preparations

Plastic Containers for Non-injectable Preparations

Plastic Containers for Ophthalmic Preparations

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TESTS FOR PLASTIC CONTAINERS FOR INJECTABLE PREPARATIONS:

These tests should include :
Examination of the product to ensure absence of any

sensory, chemical or physical change.

Assessment of changes in the quantity of contents due

to permeability of the plastic.

Detection of changes in pH.

Assessment of the effects of light, chemical tests and

biological tests.
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 General Requirements
Material Characteristics

Test on Extracts
Physico-chemical Tests

Tests on Containers
Leakage test Collapsibility test Transparency

Water vapour permeability

Extractable di(2-

ethylhexyl)phthalate

Appearance Light Absorption pH, Non-volatile matter Residue on Ignition Heavy Metals Buffer capacity Oxidisable Substance

Tests

on

Material
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Biological Tests Container Systemic Injection Test Intracutaneous Test

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Barium, Heavy metals, Tin, Zinc,

Residue on Ignition
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1. GENERAL REQUIREMENTS:
Material :
Only maiden Plastic materials to be used. Practically odorless. Additives such as Antioxidants, Lubricants, Plasticizers, Stabilizers

etc. may be used but no pigment is used for purposes of coloring.

Characteristics :
The container is sufficiently transparent to allow adequate visual

inspection of its contents.

A filled container is to be sterilisable by heat or any other method

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without showing signs of shrinkage, distortion, discoloration, loss of transparency, cracking or any other kind of deterioration.

2. TESTS ON CONTAINERS:
Leakage test: Fill ten containers with water, fit with closures and keep them

inverted at room temperature for 24 hours.

There are no signs of leakage from any container. Collapsibility test: This test is applicable to containers which are to be squeezed

in order to remove the contents.

A container, by collapsing inward during use, yields at least

90% of its nominal contents at the required rate of flow at ambient temperature.
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 Transparency :
Prepare a 16-fold dilution of the suspension prepared

for the standard suspension to give an absorbance.

Fill five empty containers to their nominal capacity with

the diluted suspension (gives an absorbance of 0.37 to 0.43 at 640 nm).

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.

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 Water vapour permeability :

Fill five containers with the water and heat-seal the

bottles.
Weigh accurately each container and allow to stand

for 14 days at a relative humidity of 60 5% and a temperature between 20 and 25.

Reweigh the containers. The loss in weight in each container is not more than

0.2%.

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 Extractable di(2-ethylhexyl)phthalate:

Containers of plasticised polyvinyl chloride (PVC) for injectable preparations (i.v. infusions) must comply with extractable di(2ethylhexyl)phthalate test:
Fill the empty container with dilute ethanol (of relative density

0.9373 to 0.9378), container.

remove the air completely from the

Place container in a horizontal

position in a water-bath maintained at 36 to 38 for 60 minutes without shaking. times and transfer the contents to a glass flask.

Remove the container from the water-bath, invert it gently 10 Immediately measure the absorbance at the maximum at about

272 nm.
Calculate the percentage of di(2-ethylhexyl)phthalate from a
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calibration curve obtained from the absorbance of standard QC & QA solutions of di(2-ethylhexyl)phthalate in alcohol. 13 February 2013

TESTS ON CONTAINER MATERIAL

The following tests are done on portions of the container that are unlabeled, unprinted or non-laminated or on the granules of plastic in the case of containers made by the form-fill-seal process.
Barium :
Moisten 2 g with hydrochloric acid and ignite in a platinum dish.

Dissolve the residue in 10 ml of 1M hydrochloric acid, filter and

add 1 ml of 1M sulphuric acid to the filtrate.

Any turbidity produced is not greater than that produced on adding

1 ml of 1M sulphuric acid to a mixture of 10 ml barium standard solution (10 ppm Ba) and 10 ml of 1M hydrochloric acid.
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 Heavy metals :
Take 2.5 g & add 20 ml of sulphuric acid and heat for 10 minutes. Add hydrogen peroxide solution dropwise to the hot solution until it

becomes colorless.
Cool, transfer to a platinum dish and evaporate to dryness. Dissolve the residue in 10ml of 1M hydrochloric acid and add

sufficient water to produce 25 ml (solution A).

To 10 ml of solution A, add 2 ml of acetate buffer pH 3.5 add 1.2 ml

of thioacetamide reagent, mix and allow to stand for 2 minutes.

Any yellow color in the solution is not more intense than the yellow

colour obtained by repeating the operation using 10 ml of cadmium standard solution (10 ppm Cd) in place of solution A.
Any brown color in the solution is not more intense than that

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obtained by repeating the operation using a mixture of 5 ml of lead standard solution (10 ppm Pb) and 5 ml of water in place of solution QC & QA 13 February 2013 A.

 Tin : To 10 ml of solution A obtained in the test for Heavy

metals add 5 ml of sulphuric acid (20%), 1 ml of a 1% w/v solution of sodium dodecyl sulphate and 1 ml of zinc dithiol reagent.
Heat in a water-bath for 1 minute, cool and allow to

stand for 30 minutes.

Any red colour in the solution is not more intense than

the red colour obtained by repeating the operation using 10 ml of tin standard solution (5 ppm Sn) in place of solution A.

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 Residue on Ignition :
Take 5 g of the sample in a suitable tared crucible. Ignite to constant weight in a muffle furnace at 8000+

250.
Allow the crucible to cool in a desiccator. It should not be more than 0.1%.

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 Zinc :
To 1 ml of solution A obtained in the test for Heavy metals

add sufficient water to produce 100 ml .

Take 10 ml of the resulting solution (test solution) add 5 ml

of acetate buffer solution pH 4.4 , 1 ml of 0.1M Sodium thiosulphate and 5 ml of 0.001% w/v solution of dithizone in chloroform, shake and allow to stand for 2 minutes.
Any violet colour in the chloroform layer is not more

intense than that obtained by repeating the operation using a mixture of 2 ml of zinc standard solution (10 ppm Zn) and 8 ml of water in place of the test solution.
Carry out a blank determination using 10 ml of water in

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place of test solution. The test is not valid unless the chloroform layer obtained in the blank determination is 13 February 2013 QC & QA colourless.

TEST ON EXTRACTS:
The following tests are based on the extraction of the plastic material, Take a portion plastic material and sub-divide into strips approximately

5 cm long and 0.3 cm wide.

Take the strips in a 250ml, graduated cylinder of Type I glass, and wash

with purified water

Transfer to a suitable extraction flask and add 200 ml of purified water

and extract by heating in a water-bath at 700 for 24 hours or heat in an autoclave at 121 for 30 minutes and cool.
Transfer 20.0 ml of the extract into a suitable container. Use this portion

in the test for Buffering capacity.

Immediately decant the remaining extract into a suitable clean container

and seal.
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Use purified water where a blank is specified in the following tests.

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 Appearance:
The extract is colourless and is clear.

Light absorption:
The light absorption of the extract, using water as the

blank is not more than 0.08 in the range 220-240 nm and not more than 0.05 in the range 240-360 nm.
pH :
To 20 ml each of the extract and the blank add 1 ml of a

0.1% w/v solution of potassium chloride and determine the pH of the solutions. The difference in pH of the two solutions is not > 1.5.
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 Non-volatile matter: Transfer 50.0 ml of the extract to a suitable tared silica crucible Evaporate on a water-bath and dry the residue at 1050 for 1

hour. Repeat the operation with the blank the difference between the residues obtained form the extract and the blank does not exceed 15 mg .
NOTE If an oily residue is expected, inspect the crucible

repeatedly during the evaporation and drying period, and reduce the amount of heat if the oil tends to creep along the walls of the crucible.
Buffer Capacity: Titrate the previously collected 20 ml portion of the extract to a

pH of 7.0 with 0.01M hydrochloric acid or 0.01M sodium hydroxide.

Determining the end-point potentiometrically.
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QC & QA the operation with 20 ml of the blank. The difference Repeat

 Heavy Metals : Transfer 20.0 ml of the extract into one of the two matched

Nessler cylinders
Adjust the pH to between 3.0 and 4.0 with 1M acetic acid or 5

M ammonia
Dilute with water to about 35 ml and mix. Into the second Nessler cylinder add 2.0 ml of lead standard

solution (1 ppm Pb) and 20 ml of the blank

Adjust the pH to between 3.0 and 4.0 with 1M acetic acid or 5

M ammonia, dilute with water to about 35 ml and mix.

To each cylinder add 10 ml of a freshly prepared hydrogen

sulphide solution, dilute with water to 50 ml and mix

Any brown color produced within 10 minutes in the cylinder

containing the extract is not more intense than that in the cylinder containing the lead standard solution.
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 Oxidisable substance :
Transfer 20.0 ml of the extract into a glass-stoppered flask,

add 20.0 ml of 0.002M potassium permanganate and 1 ml of dilute sulphuric acid and boil for 3 minutes.
Cool, add 0.1 g of potassium iodide, mix by shaking and

allow to stand for 10 minutes in the dark.

Titrate with 0.01M sodium thiosulphate using 0.25 ml of

starch solution, added towards the end of the titration, as indicator.

Repeat the operation with the blank the difference between

the two titration is not more than 1.0 ml .

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References:
Jack Cooper, WHO consultant, Plastic

containers for Pharmaceuticals Testing and Control, World Health organization, Geneva, 1974. Indian Pharmacopoeia 2010 , Volume I, The Indian Pharmacopoeia Comission, Ghaziabad, Page no ; 685- 690.
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