Stability mechanisms Flashcards
What does LogP indicate?
How a drug partitions between water and octanol.
Does LogP give any indication of how long it takes to establish an equilibrium?
No
What is kinetics?
Measures the rate at which the concentration of a reactant or product changes
What are rate laws?
Relationships between the rate of reaction, concentration of reactants (and/or products) and the rate constant
How can rate be expressed?
rate = k[A]^m [B]^n
Is it easy to measure the initial rate of a reaction?
No, it involves small changes in concentration occuring over a short period of time
What is the definition of a zero order reaction?
A reaction that proceeds at a constant rate and is independent of the concentration of reactant, A.
What are examples of zero order reactions?
Elimination of alcohol
Suspensions of poorly soluble drugs e.g. calpol
What are the units of k for a zero order reaction?
mol/l-1/s-1 i.e conc/time-1
What is the definition of a first order reaction?
Reaction proceeds at a rate that is dependent on the concentration one reactant. A
What are examples of first order reactions?
Most drugs are eliminated this way
What are the units of k for first order reactions?
s-1 i.e time-1
What are pseudo first order reactions?
Some reactions involve more than one reacting species and still follow first order kinetics
What is an example of a pseudo first order reaction?
When one of the reactants is in large excess and its change in concentration during the reaction is negligible e.g. ester hydrolysis - water is in large excess compared to drug
What is the definition of half life?
The time it takes for the concentration of the reactant to decrease by half of its original value
What is meant by the stability of pharmaceutical products?
The capability of a formulation in a specific container closure system to remain within its physical, chemical, microbiological, therapeutical and toxocological specification throughout its shelf life
What is the definition of shelf life?
The time during which the product retains the same properties and characteristics it possessed when manufactured
What is stability testing used for?
Provides evidence as to how the quality of the drug product varies with time.
Establishes shelf life
Determines recommended storage conditions
Determines container closure system suitability
What are the routes of chemical degredation of medicines?
Hydrolysis - many factors increase risk of this (pH, buffer, solvent, heat, drug conc)
Oxidation
Photolysis
Chelating agents may form unwanted complexes
Why is stability testing necessary?
Chemical degredation leads to degredation of drug conc in dosage form Toxic product may form Provides assurance to patient Economic considerations Legal requiement
Apart from microbiological/toxicological tests, what other tests are solid medicines submitted to?
Heat
Moisture uptake
Physical stress
What is accelerated stability testing?
Reflects the need for a rapid evaluation of the kinetics of decomposition. It assess drug stability - uses arrhenius equation for this
What is the most common test for accelerated stability testing?
Temperature is the most common test - Maxwell Boltzman distribution - increase in temp - increase in probability of collisions
How is decomposition related to increase in temperature?
Decomposition is increased between 2 and 5 fold for each 10 degree increase in temp
What is the Arrhenius equation used for?
Used to predict the shelf life of a drug
Wha assumptions are made when using the arrhenius equation?
The mechanism of decomposition does not change with temperature therefore can extrapolate information (not alwayds true though)
How do you determine the shelf life from the arrhenius equation?
The shelf life is the time it takes for 90% of the initial amount of drug to remain
Apart from microbiological/toxicological tests, what other tests are liquid medicines submitted to?
Light (UV)
pH
Oxidation
