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
How to stabilize pharmaceutics according to
Temperature
Solvent
Acid-base catalysis
Light
Oxygen
Temperature: low
Solvent: non-aqueous, or solids
Acid-base catalysis: use pH buffer
Light: minimize light exposure
Oxygen: smaller size containers, add antioxidants, chelating agents, sealing container with N2 (inert gas)
What is stability testing established by?
International conference on harmonization
What is accelerated stability test?
High temp, high humidity
-decreases the submission time from 12 month to 6 months
Explain stress testing
“forced degradation”
Separate degradation product from available drug to find out how much drug is left
BUD dates for
non-aqueous
Aqueous, oral
Aqueous, topical
non-aqueous: 6 months
Aqueous, oral: 14 days
Aqueous, topical: 30 days
What are the 4 testing steps. Explain them
- Stability of drug SUBSTANCE
- determining mechanism & condition of breakdown + products of degradation - Stability of drug PRODUCT
- storage, excipient compatibility, - Stability of large-scale batches
- each batch is 1/10 of commercial batches
- each batch is prepared and tested the same way - Stability of COMMERCIAL batches
- ensure that every dose from each batch is within specification limits during shelf life
