Introduction
It is important to study the stability of pharmaceutical products and to know stability testing techniques for three main reasons:
- From the point of view of safety of the patient. It is important that the patient receives uniform dosing of the prescribed drug throughout its shelf-life and particularly throughout the duration of treatment. Again although most have been shown to be safe
to use from various kinetic studies, the decomposition products may not be so safe to use. So it’s the responsibility of the drug manufacturer to at least minimize, if not totally prevent the decomposition of the products. This is of particular significance with parenteral products, since injections involve; a greater risk than other forms of drug administration. - Legal requirements must consider the acceptable identity, strength, purity and quality of the drug product as specified in the official manuals and good manufacturing practice
(GMP). - Quite apart from conforming with legal requirements, it makes economic sense for a manufacturer to prevent marketing of unsafe drugs. The sale of such unstable product is hardly the best of advertisement for a manufacturer and the withdrawal and subsequent reformulation of the drug may result in considerable financial loss.
Definition
Physical degradation of pharmaceutical products is the degradation which results into the change of physical nature of drug.
Factors Effecting Physical Degradation of Pharmaceutical Products
The following are factors effecting physical degradation of pharmaceutical products:
- Loss of volatile constituents
- Loss of water
- Absorption of Water
- Crystal Growth
- Colour Changes
- Polymorphism
1. Loss of Volatile Constituents
Many drug substances are volatile at room temperature and as such may be lost from
pharmaceutical preparations where they may constitute the active drug. For example,
iodine, camphor, menthol, alcohol and ether, even tablets containing nitroglycerin may lose potency because of the volatilization of the drug. Storage in well-closed containers provide adequate protection from this problem as well as cool storage.
2. Loss of Water
Evaporation of water from liquid and semi-solid oil-in-water emulsions may cause cracking of these systems. Loss of water from aqueous solutions will give rise to concentration, and possibly crystallization of the solute. In addition some salts e.g. borax, caffeine, sodium sulphate, quinidine sulphate and sodium carbonate are efflorescent. The tendency for these
materials to lose water will depend upon the humidity and temperature of the environment.
The result will be a decrease in weight with a corresponding increase in potency of the
materials. Water loss may be prevented by storing the materials in well-closed containers.
3. Absorption of Water
The absorption of moisture from the atmosphere is a common cause of deterioration of a variety of products. For example glycerin suppositories will absorb moisture and become opaque, while gelatin capsule will soften. Some salts are deliquescent while other materials
are hygroscopic. On the other hand effervescent tablets and granules will react prematurely in a moist environment. These forms of deterioration can be prevented by storage in well closed containers.
Water Loss/Absorption – terms to note
- Efflorescence: This involves the loss of water by the solid material to form a lower hydrate or even to become anhydrous.
- Deliquescence: The process whereby water vapour is taken up by the solid material from the surrounding, atmosphere to form higher hydrates and eventually for a liquid phase.
- Hygroscopicity: Similar as above except that the solid material still remains a solid only more hydrated
- Effervescence: The process involves the release of CO2 gas upon the addition of water with a fizzling sound.
4. Crystal Growth
The precipitation of crystals from aqueous solution occurs when the vehicle becomes supersaturated with respect to the solute. In suspensions of finely divided solids, growth of the crystals is also undesirable. There is a tendency to form a compact hard cake which is difficult to re-disperse.
Prevention, or reduction of crystal growth may be achieved by avoiding the use of the
metastable form of a drug (polymorphism), and storing in an environment with minimum temperature fluctuation.
To minimize the effect of temperature fluctuations, suspensions should ideally be confined to insoluble solids, or to solids whose solubility does not greatly increase with rise in temperature.
5. Colour Changes
A colour change or fading of a pharmaceutical product is usually just a visual sign that some form of degradation is occurring (chemical or photochemical).
Medicines are often coloured for aesthetic reasons and colour fading is a fairly common source of instability. An attempt has been made to reduce the amount of fading by incorporating an UV light-absorbing compound in the tablets formulated with dyes which tend to fade when exposed to light.
6. Polymorphism
Polymorphs are different crystal forms of the same compound .Polymorphs differs from one another in the crystal energies, the more energetic ones converting to the least energetic or most stable one. Different polymorphs of the same drug may exhibit different solubility and melting points.