2. INTRODUCTION
CHEMICAL KINETICS is the study of rate of
chemical changes taking place during
chemical reactions. As applied to
pharmaceutical formulations, this includes a
study of the physical and chemical
reactions in drugs and dosage forms,
factors influencing the rate of these
chemical reactions, accelerated stability
testing and prediction of shelf life of
formulations.
3. RATE AND ORDER OF
REACTIONS
The rate of a chemical reaction is defined
as the velocity with which a reactant or
reactants undergo chemical change. The
rate of a reaction can therefore be
measured by measuring the change in the
concentration of reactant or product in a
particular period of time.
4. ZERO ORDER
REACTION
When the rate of
reaction is
independent of the
concentration of
reacting species. The
reaction is said to be
a Zero-order reaction.
The rate of the zero-
order reaction is given
by:
−
𝑑𝐴
𝑑𝑡
= 𝑘
5. FIRST ORDER
REACTION
When the rate of
reaction is directly
proportional to the first
power of the
concentration of a
single reactant, the
reaction is said to be of
first order with respect
to the single reactant.
The Rate of the First
order reaction is given
by:
−
𝑑𝑐
𝑑𝑡
= 𝑘𝑐
6. SECOND ORDER
REACTION
A reaction is said to be
second order if the
experimentally
determined rate of
reaction is proportional
either to the second
power of the
concentration of a single
reactant or to the first
power of the
concentration if the two
reactants.
If A + B = Products
then, Rate of Reaction is
𝑑𝑥
𝑑𝑡
= (𝑎 − 𝑥)(𝑏 − 𝑥)
7. PSEUDO FIRST ORDER
REACTION
In a second order reaction, if the
concentration of one reactant is in such
large excess that it virtually remains
constant, then the rate of change of
concentration follows first order. Hydrolysis
reactions ( acid or base catalysed )are
common examples of pseudo first order
reactions.
8. PSEUDO ZERO ORDER
REACTION
A compound decomposing in solution
exhibits a first order reaction but if more of it
is present as insoluble excess, then an
equilibrium is maintained between the
compound in solution and that in the solid
form. The concentration of the compound
in solution, thus, remains essentially constant
till any of the insoluble drug material
remains. Such a reaction is apparent zero or
pseudo zero order reaction.
10. COMPLEX REACTIONS
Many chemical reactions encountered in the
pharmaceutical field are not simple reactions of the
zero, first, second or third order but consists of a
combination of two or more reactions. Such
reactions are known as complex reactions. Although
the overall reaction can be characterised by the
order of the intermediate steps, more often, the rate
equation is a complicated function involving first,
second or third order intermediate steps.
Complex reactions may be classified as :-
Reversible Reactions
Parallel or Side Reactions
Consecutive or Series Reactions
11. FACTORS AFFECTING RATE
OF REACTION
Temperature
Light
Solvent
Ionic Strength
Dielectric Constant of Solvent
Catalysis
Surfactants
12. STABILITY TESTING
A study of drug stability and of stability
testing techniques is essential for the
following main reasons :-
Patient Safety
Drug Activity
Legal Requirement
Bad Image for the Manufacturer
Patient Economy
14. ACCELERATED STABILITY
ANALYSIS
Accelerated stability analysis is designed to
predict stability and hence shelf life of
formulations under normal or
recommended storage conditions by
carrying out the study under accelerated
conditions of temperature, moisture and
light.
15. STABILITY OF SEMI-SOLID
DOSAGE FORMS
Stability of active ingredients incorporated into
ointments or creams often depends upon the nature of
ointment or cream base used in formulation. Cream
bases being emulsions containing water are more
prone to decomposition of drugs which proceeds via
hydrolysis. Incorporation of drugs into gel structure
frequently leads to a change in their stability. Penicillin
G sodium has been shown to undergo increased
degradation in hydrogels of various natural and semi-
synthetic polymers. In our country coconut oil or
cosmetics creams such as cold cream are sometimes
used as a diluent for ointments and creams. However,
no data is available to indicate whether such dilutions
are safe with respect to the stability of the drug.
16. STABILITY OF SOLID
DOSAGE FORMS
The decomposition of drugs in solid dosage
forms is more complex than that occurring in
the pure drug. The situation is more complex in
multi-drug dosage forms.
The effects of various factors on the stability in
solid dosage forms :-
Temperature
Moisture
Chemical Interactions
17. ICH AND WHO GUIDELINES
FOR STABILITY STUDIES
ICH GUIDELINE TITLE
Q1A(R2) Stability Testing of New Drug Releases and
Products (Second Revision)
Q1B Stability Testing: Photostability Testing of
New Drugs Substances and Products
Q1C Stability Testing for New Dosage Forms
Q1D Bracketing and Matrixing Designs for
Stability Testing of Drug Substances and
Products
Q1E Evaluation of Stability Data
Q1F Stability Data Package for Registration
Application in Climatic Zones III and IV
18. -: MADE BY :-
MOUMITA BANERJEE
MANISHA KHANDELWAL
JUHI SINGH
