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Drug Stabilities
Drug Stabilities
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has been withdrawn.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.
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