L12 - Chemical Kinetic And Stability Of Dosage Forms 2

Question 1

What is second order kinetics?

Answer 1

The rates of bimolecular reactions, which occur when two molecules come together to form the product

Question 2

What are the two possibilities for rate in second order reactions?

Answer 2

• rate is proportional to the product of two equal concentrations
• rate is proportinal to two different concentrations

Question 3

What are the methods of determining reaction order?

Answer 3

• substitution method
• shelf life method
• graphical method

Question 4

How to use the substitution method to determine reaction order:

Answer 4

Substitute degradation data data into the rate equations to see which they fit with

Question 5

How to use the shelf life method to determine reaction order:

Answer 5

Zero order: increasing [A]0 increases t95%
First order: [A]0 and t95% are independent
Second order: increasing [A]0 decreases t95%

Question 6

How to use graphical method to determine reaction order:

Answer 6

Plot all as first order
- zero order = downwards curve
- first order = straight line
- second order = upwards curve

Question 7

What are the factors affecting reaction rate?

Answer 7

• temp
• pH
• pressure
• catalyst
• solvent
• ionic strength
• relative humidity (RH)
• excipients
• light

Question 8

What is the salt effect?

Answer 8

When non-reacting or inert ionic specied can affect the rate of drug degradation

Question 9

What is the effect or ionic strength studied?

Answer 9

• electrolytes are often added to drug solutions
• rate can also be affected by the conc of ions such as H+ or OH-

Question 10

Why does pH have a significant effect on the apparant rate constant?

Answer 10

Hydrolysis is often catalysed by H+ ions/OH- ions (specific acid/base catalysis)

Question 11

What may buffering protect?

Answer 11

Drugs from specific acid or base catalysis
- other acidic/basic buffer components ay catalyse hydrolysis (general acid-base catalysis)

Question 12

What do you determine to optimise formulation?

Answer 12

• Degradation rate constant over a range of pH values
• Plot k vs [Buffer] across the range

Question 13

How to determine when the drug is most stable?

Answer 13

Plot pH vs k (at [buffer] = 0)

Question 14

What do you need for a reaction to occur?

Answer 14

Molecules must come into contact with each other
- molecular collisions are very rapid and happening all of the time

Question 15

What is not responsible for changing reaction time?

Answer 15

Collision freq
As collision =/ reaction

Question 16

What is energy of activation (Ea)?

Answer 16

Certain critical energy that molecules require for them to react together

Question 17

What is the van’t HOff isochore eqn?

Answer 17

lnk = -deltaH/RT + deltaS/R

Question 18

What is the arrhenius equation?

Answer 18

k = A exp(-Ea/RT)

k - rate constant
A - arrhenius factor
Ea - activation energy
R - universal gas contant (8.314 Jmol-1K-1)
T - absolute temperature (K)

Question 19

What is pre-exponential factor (A)?

Answer 19

Related simply to the fraction of molecules having sufficient energy, combined with steric effects

Question 20

What happens to the proportion of molecules with sufficient energy to undergo a chemical reaction if you increase temperature?

Answer 20

Proportion of molecules with sufficient energy to undergo chemical reaction increases

Question 21

What does accelerated stability testing reject and enable?

Answer 21

• unsatisfactory formulations early in development
• rapid detection of deterioration
• prediction of shelf life
• rapid quality controol

Question 22

What do the stability testing protocols need to define?

Answer 22

• temp and humidity storage
• storage time before sampling
• num of batches to be sampled
• num of replicates within each batch
• suitable light challenge
• details of assay

Question 23

What does stress testing of a drug substance help identify?

Answer 23

• the likely degradation products
  = helps establish pathways and the intrinsic stability of the molcule and validates the stability indacting power of analytical procedures used

Question 24

What is the nature of the stress testing dependent on?

Answer 24

The individual drug substance and the type of drug product involved

Question 25

What should stress testing include?

Answer 25

• effect of temp
• humidity
• oxidation
• photolysis of the drug substance
• susceptibility of drug substance to hydrolysis

Question 26

What does the slope equal in arrhenius plots?

Answer 26

Slope = -Ea/R