The document discusses drug stability and stability analysis. It states that the stability of a pharmaceutical preparation is its ability to remain within specifications throughout its shelf life. The period between manufacture and expiry date is called the label shelf-life, and stability analysis determines this shelf life. Stability testing provides evidence of how quality varies over time and establishes storage conditions and container suitability.
1. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
Drug Stability
2. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
Stability
βStability of a pharmaceutical preparation is the capability of a
formulation in a specific container-closure system to remain within its
physical, chemical, microbiological, therapeutic and toxicological
specifications throughout its shelf life.β
ο§ The period between the date of manufacture and expiry date is
known as the label shelf-life.
ο§ The process in which the shelf-life is determined is called as
stability analysis.
3. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
Watch this video for
a better understanding
https://youtu.be/E1I37E8bThE
4. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
Products characteristics Affected by instability
ο§ Spoilage
ο§ Flavor
ο§ Texture
ο§ Appearance
ο§ Functionality
Why Stability studies are necessary ?
ο§ Chemical degradation of the product leads to lowering of the
concentration of the drug in the dosage form.
ο§ Toxic products may be formed, due to chemical degradation of the
active ingredient.
Therefore, all pharmaceutical products are required by law to display
an expiry date on the packing.
5. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
Need for stability testing
ο§ Provide evidence as to how the quality of the drug product
varies with time.
ο§ Establish shelf life for the drug product.
ο§ Determine recommended storage conditions.
ο§ Determine container closure system suitability.
ο§ Safety point of view of patient.
ο§ Prevention of economical repercussion.
ο§ Essential quality attribute.
6. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
The branch of Physical chemistry which deals with the rate of
reactions is called Chemical Kinetics
The study of Chemical Kinetics includes :
1. The rate of the reactions and rate laws.
2. The factors as temperature, pressure, concentration and catalyst,
that influence the rate of a reaction.
3. The mechanism or the sequence of steps by which a reaction
occurs.
Chemical Kinetics
7. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
Watch this video for
a better understanding
https://youtu.be/smyFYJ2s8jQ
8. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
Applications
1. Drug stability
2. Dissolution
3. Drug release
4. Pharmacokinetics
5. Drug actions
ο§ The knowledge of the rate of reactions is very valuable to
understand the chemistry of reactions.
ο§ It is also of great importance in selecting optimum conditions for
an industrial process so that it proceeds at a rate to give maximum
yield.
10. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
where [ ] represents the concentration in moles per liter whereas βdβ
represents infinitesimally small change in concentration.
Negative sign shows the concentration of the reactant A decreases
whereas the positive sign indicates the increase in concentration of the
product B.
Units of rate
mole / liter sec
mole / liter min
mole / liter hour
11. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
Average Rate of Reaction is a Function of Time
Let us consider the reaction between carbon monoxide (CO) and
nitrogen dioxide.
CO(g)+ NO2(g) β CO2(g)+ NO(g)
The average rate of reaction may be expressed as
πΉπππ = β
π [πͺπΆ]
π π
12. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
Conc. of
CO
Time
(Sec)
0.100 0
0.067 10
0.050 20
0.040 30
0.033 40
The concentration of CO was found experimentally every 10 seconds. The
results of such an experiment are listed below.
Average rate
mole . l-1 s-1
0
0.0033
0.0017
0.0010
0.0007
β
π πͺπΆ
π π
=
β π. πππ β π. πππ
ππ β π
=
π. πππ
ππ
= π. ππππ ππππ πβππβπ
13. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
Rate laws
ο§ At a fixed temperature the rate of a given reaction depends on
concentration of reactants.
ο§ The exact relation between concentration and rate is determined
by measuring the reaction rate with different initial reactant
concentrations.
ο§ By a study of numerous reactions it is shown that :
βthe rate of a reaction is directly proportional to the reactant
concentrations, each concentration being raised to some power.β
15. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
An expression which shows how the reaction rate is related to
concentrations is called the Rate law or Rate equation.
The power (exponent) of concentration n or m in the rate law is usually a
small whole number integer (1, 2, 3).
The proportionality constant k is called the rate constant.
Examples of rate law :
18. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
Chemical reactions may be classed into two types :
(a) Elementary reactions
(b) Complex reactions
An elementary reaction is a simple reaction which occurs in a
single step.
A complex reaction is that which occurs in two or more steps.
Types of a reactions
19. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
Molecularity of a reaction
20. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
Molecularity of an Elementary Reaction
The molecularity of an elementary reaction is defined as the
number of reactant molecules involved in a reaction.
Unimolecular reactions : (molecularity = 1)
A β Product
Example:
Br2 β 2Br
21. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
Bimolecular reactions : (molecularity = 2)
A + B β Products
A + A β Products
CH3 COOC2H5 + H2πΆ β CH3 COOH +C2H5 OH
Example:
22. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
2NO + O2 β 2NO2
2NO + Cl2 β 2NOCl
Termolecular reactions : (molecularity = 3)
A + B + C β Products
Example:
23. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
Why High Molecularity Reactions are Rare ?
ο§ Most of the reactions involve one, two or at the most three molecules.
The reactions involving four or more molecules are very rare.
ο§ According to kinetic molecular theory, the rate of a chemical reaction
is proportional to the number of collisions taking place between the
reacting molecules.
ο§ The chances of simultaneous collision of reacting molecules will go
on decreasing with increase in No. of molecules.
ο§ Thus the possibility of three molecules colliding together is much less
than in case of bimolecular collision.
24. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
Molecularity of a Complex Reaction
ο§ Most chemical reactions are complex reactions. These occur in
a series of steps.
ο§ Each step is an elementary reaction.
ο§ The stepwise sequence of elementary reactions that convert
reactants to products is called the mechanism of the reaction.
ο§ In any mechanism, some of the steps will be fast, others will be
slow.
ο§ Thus the slowest step is the rate determining step of the
reaction.
25. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
The decomposition of N2O5
2N2O5 β 4NO2+ O2
It occurs by the following steps :
step 1 2N2O5 β 2NO2+ 2NO3 (slow)
step 2 NO2+ NO3 β NO + NO2 + O2 (slow)
step 3 NO + NO3 β 2NO2 (fast)
Overall reaction 2N2O5 β 4NO2+ O2
26. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
Differences Between Order and Molecularity
27. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
The molecularity and order for an elementary reaction are equal.
Molecularity and Order are Identical for Elementary Reactions
Molecularity and Order for an elementary reaction