Lecture 11 - Chemical kinetics and stability of dosage forms 1

Question 1

Why is it important that pharmaceutical products remain stable for as long as possible?

Answer 1

Chemical degradation leads to the loss of active product- loss of potency and potentially toxic degradation.

instability can also lead to reduced solubility and bioavailability.

Question 2

Name five mechanisms of degradation of drugs

Answer 2

hydrolysis, oxidation, isomerization, photochemical degradation, polymerisation.

Question 3

Hydrolysis is the most common pathway for drug breakdown. Why drugs may be degraded through hydrolysis?

Answer 3

aspirin, procaine (esters), penicillin’s (amide, lactam) and benzodiazepines (lactam)

Question 4

Hydrolysis of drugs may be ……… or ……….. catalysed

Answer 4

H+
OH-

Question 5

It may be possible to modify drug structure to prevent….

Answer 5

hydrolysis

Question 6

Oxidation is common in drugs like…

Answer 6

steroids and sterols and polyene antibiotics (C=C), ethers and sulphur groups

Question 7

Oxidation commonly occurs via

Answer 7

peroxy radical- ROO.

Question 8

Oxidation can be catalysed by…

Answer 8

Can be catalysed by action of UV, heat or trace metals

Question 9

Describe izomerization

Answer 9

Racemization- a pure enantiomer becomes a racemic mixture

Question 10

Describe photochemical degradation. How can it be prevented?

Answer 10

amber glass to block UV- tablets can be coated with a UV absorbing polymer

Question 11

Polymerisation of drugs occurs at ….

Answer 11

high concentration

Question 12

give four routes of degradation.

Answer 12

1. Direct (A –> B where K is the rate constant). This is what we will look at
2. Dynamic equilibrium
3. Competitive
4. Sequential

Question 13

What is the molecularity of a reaction??

Answer 13

the number of reactant molecules or ions which participate in the rate determining step

Question 14

Molecularity of reaction:
Reactions maybe unimolecular, bimolecular or even termolecular. Give rate equations of each

Answer 14

Termolecular = Rate = [A]^3

Question 15

Termolecular reactions are very rare in ………. . They occur more commonly in…?

Answer 15

solution
gas phase

Question 16

What is the law of mass action?

Answer 16

When you have a number of reactants reacting together, the rate = rate constant multiplied by the concentration of reactants raised to a power equal to the number of molecules.

Question 17

What does the order of reaction tell you?

Answer 17

tells you how the reactants concentration effects rate.

Question 18

If you double the concentration of a reactant and the rate stays the same, the order with respect to that reactant is……..

Answer 18

0

Question 19

If you double the concentration of a reactant and the rate doubles, the order with respect to that reactant is…

Answer 19

1

Question 20

If you double the concentration of a reactant and the rate quadruples. the order with respect to that reactant is…

Answer 20

2

Question 21

The overall order of reaction =

Answer 21

the sum of the powers of the reactants in the rate equation

Question 22

We cannot just observe an equation to find order, we need to…

Answer 22

know the individual order of each reactant and we do this through experimentally working them out

Question 23

The order is usually as small whole number but it can be….?

Answer 23

a fraction or zero

Question 24

give the basic rate equation for a first order reaction.

Answer 24

• Rate= K[A]1

Question 25

How could you find the rate of a first order reaction using a concentration-time graph? Write an equation for this.

Answer 25

The gradient of the tangent of the concentration-time graph of the first order reaction is the rate. The change in [A] divided by the change in time = Rate. Rate = (Δ[A])/ΔT = K[A]

Question 26

What is the integrated first order rate equation?

Answer 26

Question 27

The units of the rate constant depend upon the

Answer 27

order of reaction use the units given

Question 28

K is always...

Answer 28

positive

Question 29

Integrated equation for rate constant for a first order reaction

Answer 29

Question 30

First order half life: At half life, how much of the drug remains?

Answer 30

HALF the concentration of the drug

Question 31

Half life for first order reaction equation

Answer 31

Question 32

Define shelf life.

Answer 32

Shelf life of a medicine is the time that a specific drug characteristic remains within a particular specification after manufacture when stored according to the label.

Question 33

Shelf life can be based upon one of two things..

Answer 33

- Can be based on the amount of drug remaining or the accumulation of degradation product.

Question 34

shelf life may be estimated mathematically through

Answer 34

extrapolation

Question 35

In our lectures, shelf-life was defined as...

Answer 35

95% of the label dose.

Question 36

Give equation for shelf life of first order reaction.

Answer 36

Question 37

In a first order reaction, shelf life is intendent of...

Answer 37

initial concentration of the drug.

Question 38

We can find the ratio between half life and shelf life. Give the equation for first order.

Answer 38

Question 39

Give the step by step method to find k, half life and shelf life using time and concentrations of a drug.

Answer 39

Calculate ln values from the data Plot ln of residual % drug versus time on linear graph paper Calculate rate constant k from slope (m = -k) Calculate half-life (t½ = 0.693 / k) Calculate shelf-life (t95% = 0.0513 / k)

Question 40

Describe untrue/pseudo zero order. Use suspensions to explain.

Answer 40

- In a 1st order reaction, the rate decreases throughout the reaction because the concentration of A decreases. - But, if drug A could be replenished, the rate would be a constant. For example, suspensions. - In suspensions, there are solid undissolved particles and also a percentage of the drug in solution. The drug will only degrade in solution. - A in solution is replenished by dissolution of solid drug particles- this keeps the concentration of A constant.

Question 41

pseudo/untrue zero order: The constant concentration = constant rate. Therefore, what would the concentration-time graph look like?

Answer 41

straight line with negative gradient.

Question 42

What is the integrated zero order equation?

Answer 42

Question 43

Graphical zero order K equation

Answer 43

Question 44

Zero order half life equation

Answer 44

Question 45

zero order shelf life equation

Answer 45

Question 46

In zero order, the shelf life is indepedent of.....

Answer 46

initial concentration

Question 47

Give the equation for ratio of half life to shelf life in zero order reactions

Answer 47

Question 48

in pseudo zero order reactions, once the solid particles in suspension are fully solubilized in solution...?

Answer 48

Once the solid particles in suspensions are fully solubilized in solution, the degradation will no longer follow zero order. You then get first order degradation.

Question 49

In first order reactions, a plot of ln[A] against time gives a straight line with a slope of = -k. How does this differ to zero order?

Answer 49

in zero order, a plot of [A] against time fives a straight line with a slope of = -k

Question 50

In first order, K is described in terms of seconds-1. How does this differ to zero order

Answer 50

SI units of zero order = moles, litre, seconds

Question 51

For first order, shelf life is independent of initial concentration. How does this differ to zero order?

Answer 51

Shelf life is dependent on initial concentration.