1. Chemical Stability of Drugs 13 Nov 2016
Revise:
Types of drug/formulation instability,
Importance of drug stability studies,
Factors affecting drug stability,
Definition of degradation reaction rate,
Definition of degradation reaction order,
How to determine the reaction order,
Relation between reaction rate and reaction order,
How to determine the reaction rate constant,

2. Rates and Orders of Reactions For A B , A + B C reactions rate  [A] a rate  [A] a[B] b a, a+b = the orders of the reaction Zero first OR second,.. ?? Rate = K Rate=K[A] Rate =K[A][B]

3. Slope = ? Intercept = ? T0.5=? T0.9= ? For A ------- B
Zero – Order Reactions
For A B
Slope = ?
Intercept = ?
T0.5=?
T0.9= ?

4. First Order Reactions

5. Apparent Zero Order Reactions Degradation in Suspensions
C is rendered constant in suspension, so Kc = K0, thus

6. Factors Affecting Drug Chemical Stability
Temperature The effect of temperature on reaction rate is given by the Arrhenius Equation: k=Ae-Ea/RT By taking the log of both sides, the equation transforms into: log k= logA – Ea /2.303RT

7. The pH
Specific Acid – Base Catalysis
Read the figure
Importance of the pH profile in the formulation process

8. General Acid – Base Catalysis
The catalytic effect resulting from the buffer components is called a general acid – base catalysis.
Importance of the pH profile in the formulation process

9. Modes of Pharmaceutical Degradation & Protection Methods
Hydrolysis
Hydrolysis of esters and amides is the most common example, these reactions are dependent on H+ and OH- ions as catalysts so in order to stabilize the formulation, the pH must be adjusted to match the minima in the stability-pH profile if possible.
Oxidation
Can be prevented by a variety of approaches including the manufacturing and packaging under inert conditions, addition of antioxidants (ascorbic acid, Na sulphite, metabisulfite and bisulfate), the use of chelating agents, reduction in storage temperature and formulation at optimum pH for stability.
Photolysis

10. Accelerated Stability Testing
Stability testing and shelf life determination is usually performed using accelerated stability protocols.
Accelerated stability protocols have been developed to reduce the time required to determine the products shelf life at the storage conditions.