Topic 16 - Stability Flashcards
Stability
Extent to which a product retains, throughout its use and storage, the same properties and characteristics it possessed when manufactured.
5 considerations
- Chemical
- Physical
- Microbiological
- Therapeutic
- Toxicologic
5 degradation mechanisms
- Hydrolysis
- Oxidation
- Photo-degradation
- Isomerisation
- Interactions between formulation compounds (buffers + accelerated photodecomposition)
T/F: Diff bonds in formulation have diff susceptibilities to hydrolysis
T
Examples of common drugs prone to hydrolysis degradation
Aspirin, Chloramphenicol
Hydrolysis breaks ____ and ____ bonds
Ester, amide
Oxidation is initiated by _______ _______.
Free radicals
Examples of drugs susceptible to oxidation
Epinephrine, vitamin A, ascorbic acid
T/F: In photo-degradation, the reaction rate is independent of temperature
T
Isomerisation definition
Conversion of a drug into its optical isomer
T/F: Enantiomers often have significantly different ADME and pharmacological action
T
Isomerisation is often catalyzed by what?
Acid or base (phosphate ions, citrate ions)
Factors governing stability of liquid drugs (5)
- pH
- Temp
- Ionic strength
- Solvent
- Oxygen
Factors governing stability of solid drugs
Excipients (avoid hygroscopic excipients though; polymer films can act as barriers to reduce the affect of water and oxygen degradation)
What do we need to consider when designing a buffer?
Need to design buffer to have pH closer to the injected tissue’s, or design it to have lower buffering capacity
Solvent catalysis
Minimum region of k vs. pH plot that can occur along with both acid and base catalyzed degradation
Minor influences on drug stability (3)
- Temp (increase rate of rxn)
- Solvent
- Ionic strength
Strategies to prevent hydrolysis of a liquid administered drug (4)
- optimize pH, buffer, solvent
- refridgerate
- add complexation agent
- adjust dosage form (emulsion, suspensions)
Strategy to prevent oxidation of a liquid administered drug (examples?)
Add anti-oxidants (sodium bisulfite, ascorbic acid, ascorbul palmitate, butylated hydroxytoluene (BHT))
3 major concerns of stabilizing solid dosage forms
- Moisture
- Hygroscopic excipients
- Excipient catalyzed rxns (ie. Mg stearate lubricant)
Shelf-life
The length of time a drug can stay on the shelf w/o degrading to unacceptable levels.
t_90
Time required to degrade 10% of the drug, while 90% of the drug i still active
