QUALITY CONTROL TESTING OF PACKAGING MATERIALS

 

2.1 GLASS CONTAINERS
Glass containers may be colourless or coloured. Neutral glass is a borosilicate glass containing significant amounts of   boric oxide, aluminum oxide, alkali and/or alkaline earth oxides. It has a high hydrolytic resistance and a high thermal shock resistance.

Soda-lime-silica glass is a silica glass containing alkali metal oxides, mainly sodium oxide and alkaline earth oxides, mainly calcium oxide. It has only a moderate hydrolytic resistance.

According to their hydrolytic resistance, glass containers are classified as:
– Type I glass containers which are of neutral glass, with a high hydrolytic resistance, suitable for most preparations whether or not for parenteral use,
– Type II glass containers which are usually of soda-lime- silica glass with high hydrolytic resistance resulting from suitable treatment of the surface. They are suitable for most acidic and neutral, aqueous preparations whether or not for parenteral use,
– Type III glass containers which are usually of soda- lime-silica glass with only moderate hydrolytic resistance. They are generally suitable for non-aqueous preparations for parenteral use, for powders for parenteral use (except for freeze-dried preparations) and for preparations not for parenteral use.

Glass containers intended for parenteral preparations may be ampoules, vials or bottles. The glass used in the manufacture of such containers complies with one of the requirements for hydrolytic resistance given below:-

Containers of Type II or Type III glass should be used once only. Containers for human blood and blood components must not be re-used. Glass containers with a hydrolytic resistance higher than that recommended for a particular type of preparation may generally also be used.

Containers for parenteral preparations are made from uncoloured glass except that coloured glass may be used for substances known to be light - sensitive; in such cases, the containers should be sufficiently transparent to permit visual inspection of the contents.

Glass is a common material to be used in either no sterile or sterile liquid dosage forms.  It leaches alkali from its surface.  Leaching of alkali can be reduced but cannot be zero.  Hence, a limit test for alkalinity is to be performed before using it for a particular product.

EVAUATION PARAMETERS:-
(A)       Crushed – glass test:
This test is official in USP.  The container is crushed and sieved to produce uniform particles of which a definite weight of taken.  The control of the particle size and weight of powder ensures that a constant surface area is exposed to the solution.  Because all of the glass (not just the surface layer) is examined and extraction is enhanced by the rough surfaces of the particles, this is a severe test, and, if a glass passes, it is unlikely that containers made from it will give trouble while is use.  Nevertheless, the technique is tedious and is not applicable to surface treated containers (sulphured or siliconed) because crushing would expose the alkaline glass below the surface. This test can be used for determining the nature of a glass or for distinguish between two types of glasses, such as neutral or surface – treated.

(B)       Whole-Container test:
This test is official in European, British and International Pharmacopoeias. it is used in the USP for treated soda-lime containers only.  The containers are simply filled with the test solution and exposed to the test conditions. Glassware may pass the whole container test more easily because the surface layer of a container is smooth and less reactive.

In this test, surface area does not increase as much as volume with the increase in container size, consequently, the small sized containers are more attacked by the leaching of the alkali from the surface.

Container

Surface area which supplies alkali to each milliliter of the solution.

Ampoule (1 ml.)

5.9 cm2

Ampoule (10 ml.)

2.9 cm2

Bottle (1000 ml)

0.5 cm2

(C) Chemical resistance of test
USP and IP provide two tests to determine the chemical resistance of glass containers.

Table shows limits of alkalinity for glass containers:-

Tests

Containers

Limits ml of 0.02 N H2so4

1. Powdered Glass Test

Type I

Type III

Type NP

1.0

8.5

15.0

2. Water Attack Test

type II (100ml of less)

type II (over 100ml)

0.7

0.2

(D)Powdered Glass Test
From the glass containers, alkaline constituents (oxides of sodium, potassium, calcium, aluminum, etc.) are leached into purified water under conditions of elevated temperatures. When the glass is powdered the leaching of alkali can be enhanced in the powdered is critical.

The principle involved in the powdered glass test in estimate the amount of alkali leached form the glass powder. The amount of acid that is necessary to neutralize the released alkali (a specified limit) is specified in the pharmacopoeia. The basic analysis is acid-base titration using methyl red indicator.

(E)Water Attack Test
This test is used only with containers that have been exposed to sulphur dioxide fumes under controlled humidity conditions. Such a treatment neutralizes the surface alkali. Now the glass becomes chemically more resistant. The principle involved in the water attack test is to determine whether the alkali leached form the surface of a container is within the specified limits or not. Since the inner surface is under test entire container (ampoule) has to be used. 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. Methyl red indicator is used to determine the end point. The basic is acid-base titration.

2.2 PLASTIC CONTAINERS
Plastic containers for pharmaceutical products are made from plastics based on the following polymers: polyethylene (low or high density), polypropylene, polyvinyl chloride, polystyrene and to a lesser extent polyethylene terephthalate. The containers consist of one or more polymers together with certain additives if necessary. They should be manufactured from materials that do not include in their composition any substances that can be extracted by any contents in such quantities so as to alter the efficacy or stability of the product or to present a toxic hazard. Additives may consist of antioxidants, lubricants, plasticizers and impact modifiers but not antistatic agents and mould- release agents.

Drug Plastic Consideration
1. Permeation:  The transmission of gases, vapours or liquid through plastic packaging materials can have an adverse effect on self life of drug. Permeation of water vapour and oxygen through the plastic wall into the drug can present a problem if the dosage form is sensitive to hydrolysis and oxidation. Temperature and humidity are important factors influencing the permeability of oxygen and water through plastic. An increase in the temperature increases the permeability of gas.

2. Leaching: Since most plastic containers have one or more ingredients added in small quantities to stabilize a specific to the plastic the prospect of leaching or migration from the container to the product is present. Problems may arise with plastics when coloring agents in relatively small quantities are added to the formula. Release of a constituent from the plastic container to the drug product may lead to drug contamination and necessitate removal of the product from the market.

3. Sorption: It may be defined as bonding of a solute to a plastic .This process involves the removal of constituents from the drug product by the packaging material. Sorption may lead to serious problem for drug preparation in which important ingredients are in solution. Since drug substances of high potency are administered in small doses, losses due to sorption may significantly affects therapeutic efficacy of the preparation.

4. Chemical Reactivity: Certain ingredients that are used in plastic formulations may react chemically with one or more components of a drug product. At times ingredients in the formulation may react with the plastic. Even micro quantities of chemically incompatible substance can alter the appearance of the plastic or the drug product.

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