DISCUSSION ON DRUG’S PHYSICAL STABILITY
Physical stability implies that the formulation is totally unchanged throughout its shelf life and has not suffered any changes by way of appearance, organoleptic properties, hardness, brittleness, particle size etc.
It is significant as it affects:
· pharmaceutical elegance
· drug content uniformity
· drug release rate.
Physical degradation of pharmaceutical products
Loss of volatile constituent
Iodine, camphor, menthol, alcohol , nitroglycerin and anaesthetic ether are volatile at ambient temperature and may be lost from pharmaceutical preparations.
Prevention: Volatile substances should be stored in a cool place.
Loss of water
Evaporation o 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 crystallization of the solute. Examples: Salts, e.g. borax, caffeine, sodium sulphate, quinidine sulphate and sodium carbonate are efflorescent.
Prevention: Storage in well-closed containers.
Absorption of Water
Calcium chloride, potassium citrate, potassium hydroxide, potassium carbonate are deliquescent. Glycerine, dehydrated alcohol, sulphuric acid and most dry extracts are hygroscopic. Effervescent tablets besides granules will react in a moist environment.
Prevention: storage in well-closed container.
Crystal Growth
The deposition of crystals from aqueous solution happens when the vehicle becomes supersaturated with respect to the solute.
Cause of crystal growth in suspension:
1. Temperature fluctuation: a rise causing increased solubility and a fall causing super saturation and crystallization.
2. The presence of a meta stable form of the crystals which has a greater solubility than the stable form .The solution will be supersaturated with respect to the stable form.
3. Small crystals have a greater solubility than large crystals so that the solution is super saturated with respect to the latter.
4. Change of crystal structure due to the presence of dispersing solvent.
Example: 20% w/v calcium gluconate solutions are super saturated. In tis case, calcium saccharate or calcium lactobionate is used as stabilizer.
Prevention:
- Avoiding the use of metastable form of a drug.
- Storage in an environment that exhibits the minimum of temperature fluctuation.
- A narrow size range of crystals should be used incorporation of a surface-active agent.
- Diffusion of solute molecules to the crystal surfaces may also be hindered by increasing the viscosity of the suspending medium.
- In order to minimize the effect of temperature fluctuations, suspensions should ideally be confined to insoluble solids, or, at least, to solids whose solubility does not increase greatly with rise in temperature.
Polymorphic changes
Inter conversion of polymorphic forms of a drug may cause alteration in solubility and possibly crystal growth in aqueous suspension.
Prevention: It is essential that the formulated product should contain a stable crystalline form of the drug.
Color changes
A change in color of a pharmaceutical product is usually just a visual indication that some form of chemical or photochemical decomposition is occurring. It is thus necessary to investigate and remove the cause of chemical instability. Example: Indigo carmine tend to fade rapidly in the presence of reducing agent such as lactose and dextrose.
Dyes also tend to fade when present in tabled exposed to light. An effort has been made to reduce the amount of fading by incorporation an ultraviolet light-absorbing compound in the tablet formulation.
