stability 1/2 Flashcards
(47 cards)
define stability
Stability is the ability to remain within specifications to ensure the safety, efficacy and acceptability of the medicine.
what are the 3 main factors in product stability?
–Physical stability–Microbial stability–Chemical stability
how are physical/microbial and chemical stability controlled? and how are they measured?
These factors are controlled in product design and assessed in QC.
•Measure by rate of change.
what changes in storage/medicinal could have a major impact on the stability?
–Exposure of medicine to light and/or moisture may induce chemical instability
–Transferring tablets to MCA may allow uptake of moisture affecting disintegration time
–Preparing suspension from capsules involves microbiological risk
define expiry date
means that drug can not be used after this date because the concentration of drug is decreased and become lower than therapeutic concentration.
•In addition, some products of drug degradation are toxic and harmful to patients.
why after opening the packaging will the expiry date be shorter?
as a result of the decreased concentration of drug during usage and the effects of external factors.
what is the expiry for the following after them being opened? ; eye drops/Syrups and suspension of antibiotics/
- Eye drops: can be used for one month after opening the droppers
- Syrups and suspension of antibiotics: can be used for one week by storage in room temperature and for two weeks by storage in 4C°.
which polyform has the highest melting point?
polymorph 1
how can you convert between different polymorphs?
Mechanical stress (grinding) may convert powder to different form –Conversion may occur in suspension
is the most stable polymorph always the best?
no- may be too stable sometimes
what is a suspension?
Two-phase system comprising solid particles dispersed in a liquid
–Particles 1-1000nm termed colloids
–Particles > 1 μm termed coarse suspensions
how does instability occur in suspensions?
instability due to settling
what may particularly soluble drugs do to particle size?
Partially soluble drug may change particle size if temperature fluctuates
what happens in flocculation?
Weakly bound aggregates (“flocs”)
– Force of attraction > force of repulsion
– Settle quickly
– Large sedimentation volume– Don’t cake/ easily dispersible
what happens in a deflocculated system?
• Deflocculated systems – Force of repulsion > force of attraction – Settle slowly – Small sedimentation volume – Prone to caking
what is flocculation sensitive to?
ph, ionic strength
what influences suspension stability?
Viscosity enhancers–Pseudoplastic properties are useful Electrolytes–Reduce zeta potential–Maintain stability through Brownian motion: prevent particles sticking when they collide. surfactants hydrophilic colloids preservatives/ antioxidants sedimentation rate flocculation value • Ease of redispersion • Effect of elevated temperature • Effect of temperature fluctuations • Centrifugation
what are the physiochemical properties that may effect stability?
solvent and its effect on solubility
-the ratios that they are mixed in may lead to precipitation
ph effect
how is chemical stability helpful?
Predict likely degradation based on chemical structure
– Reactivity of functional groups in the drug• Be aware of the main factors affecting degradation rate
• Suggest strategies to improve chemical stability
what are the 3 main types of chemical reaction?
– Hydrolysis– Oxidation– Photodegradation
what does an ester hydrolyise to?
carboxylic acid +alcohol/phenol- either OG attacks or =0 attacks an adjacent H
if the R groups donate electrons to the carbonyl is the ester less/ more prone to hydrolysis?
less- less delta positive and less attractive nucleophilic centre
what effects ester hydrolysis?
ph/ The stability of the leaving group affects the rate; weaker bases are better leaving groups.
if R groups are el withdrawing- increases rate/ el donating- decreases rate
what does an amide hydrolyse to?
carboxylic acid +amine
