Stability and Drug Degradation Flashcards
What does drug stability depend on?
- drug/excipient properties
- compatability with excipients
- dosage form
- manufacturing method
- packaging
- environmental conditions
What is physical stability of a drug? Give examples.
changes in the physical properties of a dosage form
- solutions: precipitation
- suspension: caking and Ostwald ripening
- emulsions and creams: creaming, cracking and Ostwald ripening
- ointments: bleeding (separation of phases)
- tablets: size, shape, colour
- capsules: high moisture content suscetiple to changes in air humidity, cross linking
- patches: appearance, adhesive properties
viscosity, pourability, spreadability, colour, odour, consistency
What can cause loss of drug or other component from a dosage form?
- evaporation of a volatile compound
- adsorption on the surface of container/closure
- adsorption into plastic or rubber container or closure
What are consequences of loss of drug or other component from a dosage form?
problems with uniformity of content
Describe evaporation in terms of drug degradation.
eg glyceryl trinitrate from tablets
expiry date decreases from 2 years to 8 weeks when opened
nothing should be added to the bottle = this would increase likelihood of evaporation
What molecules is sorption more likely for and when is it more of a consequence?
likely for non-polar moelcules
worse if conco of drug or excipient is low as losing any propportion has higher consequences
In what case is leaching of impurities/additives from packaging the worst?
if formulation contains organic solvents/surfactants
eg plasticizer from PVC bags or release of OH ions from glass containers into solution
What dose drug degradation through chemical processes cause?
- inactive products = loss of therapeutic efficacy
- toxic degradation products = risk of SE
- producing changes in products appearance
What are mechanisms of chemical drug degradation?
- hydrolysis
- oxidation
- isomerisation
- dimerisation and polymerisation
- photochemical drug degradation
When does susceptibility increase for hydrolysis?
presence of the following groups:
- ester
- amides
- lactone
- lactams
- imide
- carbamate
Why is it important to control the pH of a solution during hydrolysis?
acids or bases catalyse hydrolysis rxn
What can decrease the rate of hydrolysis of a drug?
- decreased solubility
- solubilisation in the core of surfactant micelles
- formulation as a suspension
Why is hydrolysis less likely in solid dosage forms? What has an impact of likelihood of hydrolysis in solid forms?
drug required to be in solution
creates issues and can lead to hydrolysis:
- impact of moisture content
- impact of shell material for capsules
- impact of packaging
- desiccant
What can increase susceptibility to oxidation?
presence of phenol
What is oxidative rancidity?
specific type of oxidation
unsaturated lipids more susceptible
free radicals form due to heat, light and metal impurities
