Decomposition pathways :
- Hydrolysis
- Oxidation
- Isomerization
- Epimerization
- Photolysis
- Molecular hydrolysis and Ionic hydrolysis (protolysis):
- Examples of drugs:
Protection from hydrolysis
I-Adjustment of pH using selected buffer: of pH with maximum drug stability and greatest therapeutic action
- Example: pilocarpine,buffered at pH 5 (more active as free base than its ionized form). It is also hydrolyzed rapidleyin alkaline solutions
II-Complexation :
- E.g. Complexationbetween epinephrine and plasma proteins
- E.g. benzocainecomplex with caffeine
III-Suppression of drug solubility: using esters, free forms, etc
IV-Removal of water: dry mix or non-aq. Vehicle
V-Micellarsurfactant protection
Oxidation Mechanisms:
1-removal of electrons
2-loss of hydrogen
3-reaction with molecular oxygen
4-free radicals and chain reactions
- A free radical: is a molecule or atom containing one or more unpaired electron. They tend to take electrons from other substances causing their oxidation.
- Oxidation reactions depend on:
- A-concentration of oxidizing agent
- B-Heat, Light, pH
- C-Trace amounts of heavy metal ions
- D-Oxidation/reduction potential of the drug
- NernestEquation: (the higher the acidity of the solution the higher the oxidation/red. Potential of the drug (decreased oxidation).
E = Eo+ (RT/2) + Log [H+] [OX]/[Rd]
Protection against oxidation:
1.Removal of oxygen by bubbling N2or He during filling of the solution
2.Buffering the oxdisabledrug solution to an acidic pH as possible
3.Using a solvent free from heavy metals: or using a chelating agent with it (e.g. EDTA).
4.Filling the drug into amber colored glass or opaque plastic container
5.Using suitable anti-oxidant (easily oxidisablesubstance which has a lower oxid./red. Potential than the drug
2.Buffering the oxdisabledrug solution to an acidic pH as possible
3.Using a solvent free from heavy metals: or using a chelating agent with it (e.g. EDTA).
4.Filling the drug into amber colored glass or opaque plastic container
5.Using suitable anti-oxidant (easily oxidisablesubstance which has a lower oxid./red. Potential than the drug
Examples of anti-oxidants :
Aqueous anti-oxidants:
- Sodium sulfite, sodium thiosulfate, sodium bisulfite, sodium metabisulfiteand ascorbic acid - Oily anti-oxidants:
- Hydroquinone, Butylatedhydroxyanisol(BHA), Butylatedhydroxytoluene (BHT), and alpha-tocopherol(Vit. E)
- Mechanism of action:
A-preferential oxidation (Consumable anti-oxidants)
- E.g. sulfites group
B-Chain reaction-propagation termination (non-consumable): By blocking an oxidative chain reaction caused by free radicals
E.g. ascorbic acid and Tocopherols.