W7.3_Stability Testing Flashcards
Regarding stability testing, differentiate the stress testing in active pharmaceutical ingredients (API) and finished pharmaceutical products (FPP).
- API: help identify the likely degradation products, can help establish the degradation pathways, carried out in single batch, include temperature/humidity, (oxidation/ photolysis), evaluate susceptibility to hydrolysis across different pH
- FPP: photostability testing on at least one primary batch
Regarding stability testing, differentiate the container-closure system in API and FPP.
- API: same as/stimulates packaging proposed for storage and distribution
- FPP: on dosage form packaged in primary container-closure systems proposed for marketing/ secondary container- closure systems/ semi-permeable container
Regarding stability testing, differentiate the specification in API and FPP.
- API: include testing of stability- indicating attributes (physical/ chemical/ biological/ microbiological)
- FPP: API + preservative (ex. antioxidant/antimicrobial) content, functionality tests (ex. dose delivery system)
Regarding stability testing, differentiate the storage conditions in API and FPP.
- API: thermal stability, sensitivity to moisture, long-term/accelerated studies
- FPP: under intended country’s climatic conditions, with possible specified tolerances
What are the aim, necessity, and reason for chemical and physical stability testing? State some of the common tests carried out in solid forms and aqueous solutions.
- Aim: provide evidence of quality, establish shelf life, determine recommended storage conditions and container closure system suitability
- Necessity: chemical degradation leads to degradation of drug concentration, toxic product may form
- Reason: assurance to patient/therapeutic efficiency guarantee, economic considerations/restocking, legal requirement
- Solid form: heat, humidity, physical stress
- Aqueous solution: pH, light, oxidation
Explain the routes of chemical degradation that requires testing.
- Hydrolysis by pH (H+/OH-), buffer (ions in buffer chemical components), solvent (catalysed water, co-solvent or organic solvents), heat and humidity, drug concentration
- Oxidation
- Photolysis (light causing decomposition/heat/emission of light)
- Chelating agents (bonding of ions/molecules with metal ions to form unwanted complexes)
Explain the properties of pH stability testing. Differentiate specific acid-base catalysis and general acid-base catalysis. How may pH affect some drugs? How about reconstituted drugs?
- Catalysed by H+, OH-, water, buffer components
- Specific acid-base catalysis: absence of buffer
- -d[A]/dt=(k(0)+k(H+)[H+]+k(OH-)[OH-])[A]k(0) = rate constant of water
- Lowest point on graph = most stable to store/formulate
- General acid-base catalysis: presence of buffer
- Buffer components will affect drug components and their stability
- Buffer needs to be carefully selected to avoid drug decomposition
- pH may affect oxidation of drugs (ex. adrenaline, vitamins)
- Reconstituted drugs have lower stability, thus shorter shelf life
Describe the accelerated stability testing on temperature. Explain the use of Arrhenius equation in shelf life prediction and state it.
- To evaluate kinetics of decomposition rapidly
- Higher temperature -> lower activation energy -> increase in probability of collision/ decomposition (Maxwell Boltzman distribution)
- Each 10C increase -> decomposition increased 2-5 folds
- Arrhenius equation used to predict shelf life (assuming mechanism of decomposition does not change with temperature increase)
- k=Ae^(-E(a)/RT) -> log k=log A-(E(a)/2.303R*T)
Describe how shelf life is determined from a data set of rate constants.
