Drug Stability
•Definition: Drug stability means the ability of the pharmaceutical dosage form to maintain the physical, chemical, therapeutic and microbial properties during the time of storage and usage by the patient.
•It is measured by the rate of changes that take place in the pharmaceutical dosage forms.
•Expiry date: means that drug can not be used after this date because the concentration of drug is decreased and become lower than therapeutic concentration. In addition, some products of drug degradation are toxic and harmful to patients.
•Note! After the opening of the drug container, the expiry date will be shorter as a result of the decreased concentration of drug during usage and the effects of external factors. Example:
1.Eye drops: can be used for one month after opening the droppers
2.Syrups and suspension of antibiotics: can be used for one week by storage in room temperature
and for two weeks by storage in 4C˚.
3.Tablets and capsules remain stable in the package but after removal the expiry date will change
4.Ampoules:  must be used immediately but the vials (multidose) are stable for 24 h for the presence
of preservatives.
•Factors affecting drug stability:
1.Temperature: high temperature accelerate oxidation, reduction and hydrolysis reaction which lead
to drug degradation
2.pH:
•Acidic and alkaline pH influence the rate of decomposition of most drugs.
•Many drugs are stable between pH 4 and 8.
•Weekly acidic and basic drugs show good solubility when they are ionized and they also decompose faster when they are ionized.
•So if the pH of a drug solution has to be adjusted to improve solubility and the resultant pH leads to instability then a way out of this tricky problem is to introduce a water-
miscible solvent into the product. It will increase stability by:
-suppressing ionization
-reducing the extreme pH required to achieve solubility
-enhancing solubility and
-reducing the water activity by reducing the polarity of the solvent. For example, 20% propylene glycol is placed in chlordiazepoxide injection for this purpose.
•Reactions catalyzed by pH are monitored by measuring degradation rates against pH, keeping temperature, ionic strength and solvent concentration constant. Some buffers such
as acetate, citrate, lactate, phosphate and ascorbate buffers are utilized to prevent drastic
change in pH.
•Sometimes pH can have a very serious effect on decomposition. As little as 1 pH unit change in pH can cause a change of ten fold in rate constant. So when we are formulating a
drug into a solution we should carefully prepare a pH – decomposition profile and then
formulate the solution at a pH which is acceptable physiologically and stability-wise also.
3.Moisture:
a.Water catalyses chemical reactions as oxidation, hydrolysis and reduction reaction
b.Water promotes microbial growth
4.Light: affects drug stability through its energy or thermal effect which lead to oxidation
5.Pharmaceutical dosage forms: solid dosage forms are more stable than liquid dosage forms for
presence of water.
6.Concentration:  rate of drug degradation is constant for the solutions of the same drug with
different concentration. So, ratio of degraded part to total amount of drug in diluted solution is bigger than of concentrated solution.
Stock solutions: are concentrated solutions which diluted by using (i.e. syrup 85%)
at high concentration the stability is high
7.Drug incompatibility:  reactions between components of pharmaceutical dosage forms it self or
between these components and cover of the container .
8.Oxygen: exposure of drug formulations to oxygen affects their stability
•Three stabilities of drug must be considered::
1.Physical stability
2.Chemical stability
3.Microbiologicall stability
A.Physical stability:
Physical instabilities possibilities are:
1.Crystal formation in pharmaceutical preparations:
Causes:
a.Polymorphism phenomena: i.e. Chloramphenicol (change of amorphous to crystalline
form.
b.Saturated solution: by different temperature precipitation of solute may occur.
c.In suspension: when very fine powder is used a part of suspending agent will dissolve then
precipitate as crystal.
2.Loss of volatile substances from pharmaceutical dosage forms:
Examples:
a.Aromatic waters
b.Elixirs
c.Spirits
d.Some types of tablets which contain aromatic water (Nitroglycerin tablets)
3.Loss of water:
This can be seen in the following dosage forms:
a.Saturated solution: by loss of water they become supersaturated and precipitate as
crystals is formed
b.Emulsions: Loss of water lead to separation of the two phases and change to other type
c.Creams: especially oil/water, they become dry by loss of water
d.Pastes
e.Ointments: especially aqueous base ointments
Humectants is added to the previous dosage forms which defined as hydrophilic substances added
to aqueous phase to absorb water from atmosphere and prevent its loss from the dosage forms. Examples: Glycerin
4.Absorption of water:
This phenomena can be seen in the following pharmaceutical forms:
a.Powders: Liquification and degradation may occur as a result of absorption of water
b.Suppositories which base made from hydrophilic substances as Glycerin, Gelatin, poly
ethylene glycol.
The consistency of these forms becomes jelly-like appearence
5.Change in crystalline form:
•Example: Cocoa butter which is capable of existing in four polymorphic forms.
B.Chemical stability:
•It is discussed in chemical incompatibility unit
C.Microbiological stability:
1.Contamination from microorganisms is a big problem for all formulations containing moisture but
it can be a bother in solid dosage forms also if some natural polymers are used because many natural polymers are fertile sources of microorganisms.
2.In the type of hygienic manufacture carried out today where “Quality Assurance” is a prerequisite
as per the GMP procedures, there are definite procedures to prevent microbial contamination in all formulations.
•Sources of Microbial Contamination:
1.Water
2.Air
3.Raw materials, containers and closures
4.Personnel
5.Instruments and apparatus
Sources of microbial contaminations
Water Low demand gram-negative groups: Pseudomonas, Xanthamonas, Flavobacterium, Achromobacter
Air Mould spores: Penicillium, Mucor, Aspergillus Bacterial spores: Bacillus spp. Yeasts
Raw Materials Micrococci
Earths Anaerobic spore formers: Clostridium spp
Pigments Salmonella
Starches Coliforms
Gums Actinomyces
Animal products Salmonella, Coliforms
Personnel Coliforms,
Staphylococci, Sterptococci, Coryembacteria
Packaging And Stability
•Packaging of the drug product is very important when its stability is being considered.reactive是什么药
•The immediate container and closure are particularly important in affecting product stability.
•Glass, plastic, rubber (natural and synthetic) and metal are the four types of containers commonly utilized for packing drug products.
1.Glass
•Glass is resistant to chemical and physical change and is the most commonly used material, but it has the limitations of :
1.Its alkaline surface may raise the pH of the product.
2.Ionic radicals present in the drug may precipitate insoluble crystals from the glass
3.The clarity of the glass permits the transmission of high energy wavelength of light
which may accelerate decomposition.
•All these limitations are overcome by the technologists in the following way:
1.the first problem is overcome by the use of Borosilicate glass which contains fewer
reactive alkali ions
2.Treatment of glass with chemicals or the use of buffers helps in overcoming the second
problem
3.Amber coloured glass which transmits light only at wavelengths above 470 nm is used for
photolytic drug products.
2.Plastics
•Plastics include a wide range of polymers of varying density and molecular weight, each possessing different physicochemical characteristics. The problems with plastic are:
1.Migration of the drug through the plastic into the environment.
2.Transfer of environmental moisture, oxygen, and other elements into the pharmaceutical
product.
3.Leaching of container ingredients into the drug.
4.Adsorption or absorption of the active drug or excipients by the plastic.
•For all these problems the solution is to suitably pretreat the plastic chemically. The drug product packed in the final container must be tested for stability.

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