Drug stability Flashcards
the extent to which a dosage form retains (within specific limits) throughout storage and use, the same properties/characteristics that is had when it was manufacture
stability
the time that a product (stored correctly) will maintain stability
shelf life
The end of shelf life, ≥90% of the drug is still available on the last day of expiration date (expiration condition)
Expiry date
Which type of stability determines degradation, shelf-life, and expiration date
chemical
What is evidence of for instability in these solid dosage forms
Capsules
Tablets
Powders/granules
Lozenges
Capsules
- hardening, softening
Tablets
- powdering, chipping, mottling, discolouration, fusion
Powders/granules
- caking, colour change, swelling
Lozenges
- clumping, tackiness, and discolouration
What is evidence for instability in liquid dosage forms
Solutions
Emulsions
Suspensions
Solutions
- clarity, precipitation, mold/bacterial growth, odour, loss of volume
Emulsions
- odour, colour change, creaming, phase separation, mold
Suspensions
- difficulty of resuspension, settling, uniformity, caking, crystal growth
- more stable than solutions
What is evidence for instability in semisolid dosage forms
Creams, Gels, ointments
Suppositories
Creams, Gels, ointments
- shrinkage, separation, discolouration, microbes, grittiness
Suppositories
- Softening, crystalization (polymorph), dry out/harden
What are some sources of microbial contamination? means of preventing?
- Raw materials, water
- Manufacturing environment
- manufacturing personnel
Preventing
- Sterilization
- Addition of preservatives
Which chemical groups are susceptible to hydrolysis?
Esters: aspirin, benzocaine
Amides: lidocaine, acetaminophen
Lactams: penicillin
Lactones: simvastatin, topotecan
What factors affect hydrolysis
pH, buffer salts, ionic strength, prescence of co-solvents, complexing agents, surfactants, temperature
What are the steps of oxidation? What is the goal of antioxidants
Initiation –> propagation –> Termination
- Goal is to prevent initiation or propagation by forcing termination
What antioxidants are used in hyrdrophilic vs hydrophobic drugs?
What are other ways to reduce oxidation
Hydrophilic drugs: use ascorbic acid
Hydrophobic drugs: use BHT
Other ways
- small container (less air), reduce light, choose anhydrous formulation (no water)
What are important isomerization processes
Racemization
Epimerization
Define polymerization/dimerization
Attaching multiple of the same molecule together
Define photodecomposition
Use amber container to minimize
