THE CORE OF
HEALTHCARE
EDUCATION
TOPIC: DRUG STABILITY
Presented by: C Nthoiwa 2025 c 2025
Drug Stability
Learning outcome:
By the end of this lecture the
learners should be able to:
Apply the knowledge and
understanding of the degradation
process of pharmaceutical drugs
during storage and utilize this
knowledge to minimize
degradation rate of the products.
▪ 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.
Stability is used to determine
Quality of a Recommended
Shelf life for the
drug substance storage
drug product
or drug product conditions
Why stability testing is necessary :
o Chemical degradation may lead lowering of
concentration of drug in dosage form
o toxic product may form due to
degradation of active ingredients
LABELS FOUND IN MEDICINES DEPICTING
STORAGE CONDITIONS??
FACTORS AFFECTING DRUG
STABILITY??
Factors affecting drug stability
1. Temperature:
▪ high temperature accelerate oxidation, reduction and
hydrolysis reaction which lead to drug degradation
2. Moisture:
▪ Water catalyses chemical reactions as oxidation, hydrolysis
and reduction reaction
▪ Water promotes microbial growth
3. Light:
▪ affects drug stability through its energy or thermal effect
which lead to oxidation
4. Pharmaceutical dosage forms:
▪ Solid dosage forms are more stable than liquid dosage
forms for presence of water.
5. Oxygen:
▪ exposure of drug formulations to oxygen affects their
stability
6. pH:
▪ Acidic and alkaline pH influence the rate of
decomposition of most drugs.
▪ Many drugs are stable between pH 4 and 8
Three stabilities of drug must be considered:
1. Physical stability
2. Chemical stability
3. Microbiological stability
Physical Degradation
Types of physical degradation are as : Definition:
1. Loss of volatile components
2. Loss of H2O
3. Absorption of H2O
4. Crystal growth “Degradation, which
results into the change of
5. Polymorphic changes
physical nature of the
6. Color changes drug.”
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:
o pharmaceutical elegance
o drug content uniformity
o drug release rate.
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, polyethylene glycol.
▪ The consistency of these forms becomes jelly-like appearance
▪ Depends on temp and humidity of surrounding material
e.g.
▪ Glycerin suppositories may become opaque
▪ Gelatin capsule may soften
▪ Some deliquescent salts calcium chloride, potassium citrate.
Color Changes:
Color changes are of two types.
Loss of color
▪ pH change
Development of color
▪ Exposure to light
Preventive measures:
1. Loss of volatile components:
2. Loss of water: Product should be
3. Absorption of water: placed in well-closed
container
4. Crystal growth:
For solutions
▪ Stabilizers are added
For suspensions
▪ Incorporation of surface-active agent
▪ By increasing viscosity of suspending material
Chemical instability:
Chemical Degradation
Change in the physical nature of the drug is called as
chemical degradation.
Types of chemical degradation are as under
1. Hydrolysis
2. Oxidation
3. De-carboxylation
4. Isomerization
5. Polymerization
6- Combination
7- Complexation or chelation
Hydrolysis:
▪ It is defined as the reaction of a compound with water.
▪ Major cause of degradation of drug
Factors Effecting Hydrolysis:
▪ Moisture
▪ pH
▪ Temp.
▪ Type of the solvent
Some Functional Groups Subject to Hydrolysis
Production of insoluble form of drug:
▪ By making suspensions
▪ By pH adjustment of the aqueous solution.
▪ By preparing insoluble salt of the drug.
e.g. insoluble procaine salt of benzyl penicillin
▪ By preparing “transient derivatives” of the drug.
Oxidation
Is defined as loss of electrons or gain of oxygen.
▪ Auto-oxidation: It is a reaction with oxygen of air which
occur spontaneously without other factors.
▪ Pre-oxidants: Are substances catalyze oxidation process i.e.
metals, some impurities.
Some Functional Groups Subject to Autoxidation
Factors that lead to oxidation
▪ Presence of oxygen
▪ Light: It can cause photo-chemical reactions: chemical
reaction occur in presence of light.
▪ Temperature: Elevated temperature accelerate oxidation
reaction
▪ pH : each drug has its ideal pH for stability. Any change
in pH affect drug stability and may accelerate oxidation
reaction.
▪ Presence of pre-oxidants as metals & peroxides
Protection of drugs from oxidation
▪ Addition of Antioxidants and inorganic sulfur compounds: Vitamin E,
Vitamin C, thiosulfate and polysulfide
▪ Addition of chemicals which form complexes with metals: EDTA,
Benzalkonium chloride
▪ Protection from light: Using of dark container , Storage in
dark places , Packaging with substances which absorbed
light i.e. Oxybenzene
▪ Choice of suitable pharmaceutical dosage forms which reduce
the possibility of oxidation process (solid dosage )
▪ Maintenance of pH by using buffer solution
▪ Choice of suitable solvent(rather than
water)
▪ Storage in low temperature
▪ Protection from air by using good closed containers and
replacement of oxygen by nitrogen
Polymerization
▪ In polymerization, small repeating units called monomers are bonded
to form a long chain polymer.
▪ To avoid this formaldehyde must be stored in suitable temperature
and addition of methanol 15%.
▪ Ampicillin in high temperature forms polymers which cause
allergy
Factors that induce
Polymerization
1. Temperature
2. Light
3. Solvent
4. pH
5. Impurities
Isomerization
▪ It means conversion of drug to its isomer
▪ Isomers have Identical molecular formulas but posses a
different arrangement of atoms.
Types of Isomerization
1. Optical isomerization
2. Geometric isomerization
Microbiological
stability
Microbiological stability:
Contamination from microorganisms is a
big problem for all formulations containing
moisture
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
Packaging And Stability
Packaging of the drug product is very important when its stability is being
considered
Glass, plastic, rubber (natural and synthetic) and metal are the four
types of containers commonly utilized for packing drug products.
Glass
▪ Glass is resistant to chemical and physical change and is the most
commonly used material, but it has the limitations which are
overcome by the technologists in the following way:
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.
References
M Aulton & K. Taylor. (2013). The design and manufacture of medicines.
4th Edition. Churchill Livingston
