Stability of drugs
● Hydrolysis
● Free radical oxidation
Hydrolysis
● Slow hydrolysis of esters under neutral conditions
● Hydrolysis of esters: catalysed by acid of base
Ester
● Prone to hydrolysis
○ Acid-catalysed hydrolysis
○ Base-catalysed hydrolysis
Aspirin
● Hydrolyses to salicylic acid and ethanoic acid
● Most stable at pH 2.5
○ Formulated as free acid form
Cyclic ester-containing drugs (Lactones)
● Nystatin (Oral Candida infection)
● Clarithromycin (Macrolide antibiotic)
Amide
● More stable to hydrolysis than esters
● Resonance makes amide more stable than esters
○ Peptidases
○ Amidases
Beta-lactam ring (Cyclic amide)
● Less stable
● Penicillins
Minimising hydrolysis
● More stable in the solid form
● Know pH rate profile of hydrolysis
○ Formulate medicine at a pH where rate of hydrolysis is low
● More stable at low temperatures
● Storage (Packaging)
○ Airtight container or blister packs, to keep out water
Paclitaxel (Taxol): Anticancer drug
Hydrolysis susceptible group: Ester
Free Radical Oxidation
● Hydrolysis
● Free radical oxidation
Hydrolysis
● Slow hydrolysis of esters under neutral conditions
● Hydrolysis of esters: catalysed by acid of base
Ester
● Prone to hydrolysis
○ Acid-catalysed hydrolysis
○ Base-catalysed hydrolysis
Aspirin
● Hydrolyses to salicylic acid and ethanoic acid
● Most stable at pH 2.5
○ Formulated as free acid form
Cyclic ester-containing drugs (Lactones)
● Nystatin (Oral Candida infection)
● Clarithromycin (Macrolide antibiotic)
Amide
● More stable to hydrolysis than esters
● Resonance makes amide more stable than esters
○ Peptidases
○ Amidases
Beta-lactam ring (Cyclic amide)
● Less stable
● Penicillins
Minimising hydrolysis
● More stable in the solid form
● Know pH rate profile of hydrolysis
○ Formulate medicine at a pH where rate of hydrolysis is low
● More stable at low temperatures
● Storage (Packaging)
○ Airtight container or blister packs, to keep out water
Paclitaxel (Taxol): Anticancer drug
Hydrolysis susceptible group: Ester
Free Radical Oxidation
