First-order kinetics

Whose rate is directly proportional to the concentration of the

of drugs undergoing reaction i.e. greater the concentration ,
faster the reaction.

First-order process is said to follow linear kinetics

dC
 KC
dt

Where
K = first-order rate constant (per hour)

2/7/2016 vignan pharmacy college 1

Fig. 2: Graph of first-order kinetics showing linear relationship
between rate of reaction and concentration of drug

2/7/2016 vignan pharmacy college 2

 Mixed order kinetics
In some instances, the kinetics of a pharmacokinetic
process changes from predominantly first-order to
predominantly zero-order with increasing dose or chronic
medication.
A mixture of both first-order and zero-order kinetics is
observed in such cases and therefore the process is said to
follow mixed-order kinetics.

 Since deviations from an originally linear pharmacokinetic

profile are observed, the rate process of such a drug is called
as nonlinear kinetics. 2/7/2016 vignan pharmacy college 15
Mixed order kinetics is also termed as dose-dependent kinetics as
it is observed at increased or multiple doses of some drugs.

Nonlinearities in pharmacokinetics have been observed in –

 Drug absorption (e.g. vitamin C)
 Drug distribution (e.g. naproxen), and
 Drug elimination (e.g. riboflavin).

The kinetics of such capacity-limited processes can be

described by the Michaelis-Menten kinetics.

2/7/2016 vignan pharmacy college 4

 Complex reaction
Many chemical reaction encountered in the pharmaceutical
field are not simple reaction of the zero, first, second or third
order but consists of a combination of two or more reaction .
such reaction is known as complex reaction.

Complex reaction may be classified as:

• Reversible reaction
• Parallel reaction
• Consecutive or series reaction

2/7/2016 vignan pharmacy college 5

 Factor affecting rate of reaction

•Temperature
•Light
•Solvent
•Ionic strength
•Dielectric constant of solvents
•Catalysis
•Surfactants

2/7/2016 vignan pharmacy college 6

 Kinetics of drugs decomposition
A drugs in suspension follows apparent zero order kinetics
in which the concentration of the drugs in the solution
remains constant with time.
 When the drugs in the solution degrades or lost by any
means new drugs molecules from the suspended solid
particles dissolved in the solution to keep the concentration
constant at the equilibrium solubility.
That is the solid suspended particles act as reservoir of
drugs.
2/7/2016 vignan pharmacy college 7
Acid catalysed hydrolysis of the digoxin follows pseudo
first order reaction kinetics , here the concentration of H+
remains constant . Therefore the rate slowly depends on the
concentration of digoxin.
 Hydrolysis of chlorbutanol in presence of sodium
hydroxide follows second order reaction.

2/7/2016 vignan pharmacy college 8

 Strategy of stability testing

 Strategy is important for the stability testing of any dugs to

maintain their shelf life .
To maintain the shelf life of drugs the ICH and WHO
guideline for stability testing should be followed.

 Protection against hydrolysis

 Protection against oxidation

2/7/2016 vignan pharmacy college 9

 Accelerated stability analysis

Accelerated stability analysis is design to predict stability

and hence shelf life of formulation under normal and
recommended storage condition by carrying out the study
under accelerated condition of temperature, moisture and
light.

Prediction of shelf life

Shelf life is the time period during which the dosages
form is supposed to retain its original quantity.

 The prediction is based on the2/7a/20

rr1h6 enviginuanspheaqrmuacay tcoilolegne . 22
 Stability of solid dosages form

 The decomposition of drugs in solid dosages form is

more complex than that occurring in the pure drugs.
The following are the effect of various factor on the
stability in solid dosages form:

 Temperature
 Moisture
 Chemical interaction

2/7/2016 vignan pharmacy college 11

 Types of stability studies

 Long term stability studies

 Accelerated stability studies
 Testing frequency
 Packaging and container

2/7/2016 vignan pharmacy college 12