Stability mechanisms

Question 1

What does LogP indicate?

Answer 1

How a drug partitions between water and octanol.

Question 2

Does LogP give any indication of how long it takes to establish an equilibrium?

Answer 2

No

Question 3

What is kinetics?

Answer 3

Measures the rate at which the concentration of a reactant or product changes

Question 4

What are rate laws?

Answer 4

Relationships between the rate of reaction, concentration of reactants (and/or products) and the rate constant

Question 5

How can rate be expressed?

Answer 5

rate = k[A]^m [B]^n

Question 6

Is it easy to measure the initial rate of a reaction?

Answer 6

No, it involves small changes in concentration occuring over a short period of time

Question 7

What is the definition of a zero order reaction?

Answer 7

A reaction that proceeds at a constant rate and is independent of the concentration of reactant, A.

Question 8

What are examples of zero order reactions?

Answer 8

Elimination of alcohol

Suspensions of poorly soluble drugs e.g. calpol

Question 9

What are the units of k for a zero order reaction?

Answer 9

mol/l-1/s-1 i.e conc/time-1

Question 10

What is the definition of a first order reaction?

Answer 10

Reaction proceeds at a rate that is dependent on the concentration one reactant. A

Question 11

What are examples of first order reactions?

Answer 11

Most drugs are eliminated this way

Question 12

What are the units of k for first order reactions?

Answer 12

s-1 i.e time-1

Question 13

What are pseudo first order reactions?

Answer 13

Some reactions involve more than one reacting species and still follow first order kinetics

Question 14

What is an example of a pseudo first order reaction?

Answer 14

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

Question 15

What is the definition of half life?

Answer 15

The time it takes for the concentration of the reactant to decrease by half of its original value

Question 16

What is meant by the stability of pharmaceutical products?

Answer 16

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

Question 17

What is the definition of shelf life?

Answer 17

The time during which the product retains the same properties and characteristics it possessed when manufactured

Question 18

What is stability testing used for?

Answer 18

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

Question 19

What are the routes of chemical degredation of medicines?

Answer 19

Hydrolysis - many factors increase risk of this (pH, buffer, solvent, heat, drug conc)
Oxidation
Photolysis
Chelating agents may form unwanted complexes

Question 20

Why is stability testing necessary?

Answer 20

Chemical degredation leads to degredation of drug conc in dosage form 
Toxic product may form
Provides assurance to patient
Economic considerations
Legal requiement

Question 21

Apart from microbiological/toxicological tests, what other tests are solid medicines submitted to?

Answer 21

Heat
Moisture uptake
Physical stress

Question 22

What is accelerated stability testing?

Answer 22

Reflects the need for a rapid evaluation of the kinetics of decomposition. It assess drug stability - uses arrhenius equation for this

Question 23

What is the most common test for accelerated stability testing?

Answer 23

Temperature is the most common test - Maxwell Boltzman distribution - increase in temp - increase in probability of collisions

Question 24

How is decomposition related to increase in temperature?

Answer 24

Decomposition is increased between 2 and 5 fold for each 10 degree increase in temp

Question 25

What is the Arrhenius equation used for?

Answer 25

Used to predict the shelf life of a drug

Question 26

Wha assumptions are made when using the arrhenius equation?

Answer 26

The mechanism of decomposition does not change with temperature therefore can extrapolate information (not alwayds true though)

Question 27

How do you determine the shelf life from the arrhenius equation?

Answer 27

The shelf life is the time it takes for 90% of the initial amount of drug to remain

Question 28

Apart from microbiological/toxicological tests, what other tests are liquid medicines submitted to?

Answer 28

Light (UV)
pH
Oxidation