Drug Stabilities

Presented by: Group #7

Defination:
“ The term drug stability refers to the extent to which a drug substance or product
retains, within specified limits and throughout its period of storage and use, the
same properties and characteristics that it possessed at the time of its
manufacture.”
Importance of Drug Stability Study:
The study of stability of pharmaceutical products and stability testing techniques
is important for three main reasons.
• Patient Safety
• Legal Requirement
• Financial Repercussion
Factors Affecting Product / Drug Stability:
The product stability is affected by:
• The stability of active ingredients
• Interaction between active ingredients and excipients or container or closure
• Environmental conditions
Expiry Date:
• It is the date which is fixed by the manufacturer for a certain product after which
the harmful events may result into:
I. Loss of potency
II. Development of toxicity
Degradation of Pharmaceutical Products
• Decline to a lower quality, condition or level is called as degradation.

TYPES OF PHARMACEUTICAL DEGRADATION:

There are two types of pharmaceutical degradation.
• Physical degradation
• Chemical degradation
Physical Degradation:
“It is the degradation which results into the change of physical nature of drug. The
formulation is totally changed by way of appearance, organoleptic properties,
hardness, brittleness, particle size.”
Physical degradation includes:
• Loss of volatile components
• Loss of water
• Absorption of water
 1. LOSS OF VOLATILE COMPONENTS:
• Volatile components such as alcohol, ether, camphor, iodine, volatile oil etc.
escape from the formulation e.g. Nitroglycerine from drugs evaporates
Measures to Prevent Loss of Volatile Components:
• Such products should be placed in well closed container.
• To decrease temperature as increase in temperature will increase volatility,
product should be placed in a cool place.
2. LOSS OF WATER:
• Loss of water from o/w emulsions thus the stability changes.
• Water evaporates from efflorescent salts such as Borax and sodium bisulphate
etc.
• Water evaporates causing crystal growth.
Measures to Prevent Loss of Water:
• Water loss may be prevented by storing the product in well closed container.
3. ABSORPTION OF WATER:
• Hygroscopic drugs such as glycerin suppositories absorb
• Water from atmosphere causing physical degradation.
Preventive measure for absorption of water:
• Product should be placed in well closed container
Chemical Degradation:
“It is the separation of chemical compound into elements or simpler
compounds. Change in the chemical nature of the drug is called as
chemical degradation”.
Chemical degradation includes:
• Hydrolysis
• Oxidation
• Isomerization
1. HYDROLYSIS
• Hydrolysis means splitting of pharmaceutical product by the action of water.
• It is the main problem with the pharmaceutical systems such as emulsions,
suspensions, solutions etc.
• This is carried out by water vapours from atmosphere.
• Hydrolysis is catalyzed by hydrogen ions or hydroxyl ions and also by acidic or
basic species commonly encountered as components of buffers.
• The main classes of drugs that undergo hydrolysis are the:
o Esters
o Amides
o Lactam
A. Esters Hydrolysis:
• Upon hydrolysis of esters acyl-oxygen is cleaved and acid and alcohol is produced.

• Examples of drugs undergo hydrolysis are:

• Procaine
• Tetracaine
• Atropine
• Physostigmine
• Aspirin
B. Amide Hydrolysis:
• Although amides are relatively stable than esters but these are susceptible to
specific and general acid-base hydrolysis.
• Amide hydrolysis usually involves the cleavage of the amide linkage to give an
amide giving alcohol and amine as hydrolyzed products.

Examples of drugs undergo amide hydrolysis are: 

Dibucaine
Ergometrine
C. Ring Hydrolysis:
• Compounds containing ring undergo hydrolysis to make hydrolyzed products.
• For example, β-lactam antibiotics such as penicillins which are cyclic amides or
lactams undergo rapid ring opening due to hydrolysis

E.g
• Nitrazepam
• Chlorodiazepoxide
2. OXIDATION:
• Instabilities in a number of pharmaceutical preparations are due to oxidative
degradation of the active ingredients of these preparations when exposed to
atmospheric oxygen.
• Removal of an electropositive atom, radical or electron, or the addition of an
electronegative atom or radical is called as oxidation.
• Oxidation is of two types:
o Auto-oxidation
o Photo-oxidation
A. Auto-Oxidation:
• It is the most common form of oxidative degradation that occurs in many
pharmaceutical preparations and involves a free radical chain process.
• In an auto-oxidative degradation, only a small amount of oxygen is required to initiate
the reaction and thereafter oxygen concentration is relatively important.
• The free radicals produced during the initial reaction are highly reactive and further
catalyze the reaction to produce additional free radicals and causing a chain reaction.
Drugs that undergo oxidative decomposition are:
• Ascorbic acid
• Morphine
• Epinephrine
• Heparin
B. Photo-Oxidation / Photolysis:
• Exposure to light may produce oxidation-reduction, ring rearrangement or
modification and polymerization.
• The shorter the wave-length of light, the greater is the effect of light in initiating
the chemical reaction because of higher energy.
• The thermal (induced by light) reaction may continue even after the light source
has been withdrawn.
Pharmaceutical products undergo photolysis are:
• Ascorbic acid o Riboflavin
• Cyanocobalamin folic acid
• Hydrocortisone
3. ISOMERIZATION:
• It is the process by which one molecule is transformed into another molecule
which has exactly the same atoms, but the atoms are rearranged e.g. A-B-C → B-
A-C
Types of Isomerization:
• Optical Isomerization
• Geometrical Isomerization
A. Optical Isomerization:
• A change in the optical activity of a drug may result as a change in its biological
activity.
• It is further divided into:
• Racemization: It involves the optically active form of a drug into its
enantiomorph. E.g. adrenaline solutions at low pH due to conversion of its
therapeutically active levorotatory form to the less active dextrorotatory form,
epinephrine shows the same effect.
• Epimerization: It occurs with the compound having more than one asymmetric
carbon atom in the molecule. E.g. epimerization of tetracycline in acidic
conditions to form less active epitetracycline
B. Geometric Isomerization:
• Loss of activity due to the difference in potency exhibited by Cis and Trans
isomers of some organic compounds.
• For example, Active form of VITAMIN A molecule has all Trans configuration. In
aqueous solution as a component of multivitamin preparation, in addition to
oxidation vitamin A Palmitate isomerizes and form 6-mono cis and 2, 6 di-cis
isomers, both have low potency.
THANK YOU