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CHEMICAL KINETICS & STABILITY FINAL COVERAGE

KINETICS - it deals with the stability of drugs and the mode of action of their degradation through the examination of rates of reaction and mechanism
of action.
----- mechanism by which a chemical process gets to its final state, from its initial state and the rate at which this reaction proceeds.

PHARMACEUTICAL KINETICS .It deals with the stability of drugs and the mode of action of their degradation through the examination of rates of
reaction and mechanism of reaction.

PHARMACEUTICAL IMPORTNACE
 Prediction of expiration date and shelf life
 Determination of optimum storage condition

PHARMACEUTICAL STABILITY
------Defined as the time from the date of manufacture and packaging of the formulation until its chemical or biological activity is not less than the
predetermined labeled potency or its physical characteristic have not changed.

STABILITY OF DRUGS
HALF LIFE - it is the time required for one half of the material to disappear.
T1/2 = ½ A0 / K0
SHELF LIFE
- It is the time required for 10% of the material to disappear; it is the time at which A (conc. Of drug) has decreased to 90% of its original
concentration.
EXPIRATION DATE
- It is the date on the container label of a drug product designating the time prior to the approved shelf-life specification if stored under defined
conditions and after which it must not be used.

RATE OF REACTION
It is the velocity with which the reactant or reactants undergoes chemical change and the change in concentration is determined with time.

ORDER OF REACTION
Law of Mass Action
- the rate of the chemical reaction is proportional to the products of the molar concentration of the reactants each raised to a power equal to the
number of molecules.

Type of Definition Equation/Unit

reaction

Zero-order the rate is independent of concentration of the reactant/s a / 2k

- Proportional to the initial conc. conc/time

1st order rate of reaction is dependent of the concentration of the drug remaining 0.693 / k
- Independent of concentration time-1

2nd order Either dependent or independent 1/ ak

- Proportional to the reciprocal of concentration conc-1/time-1

Other Methods of determining Reaction:

 Substitution method
 Graphic method
 Half-life method

FACTORS AFFECTING RATE OF REACTION:

 Temperature
- Increase temperature increases the rate of chemical reaction
 Change in pH (Specific acid and specific base catalysis
- Catalysis by the hydronium or hydrogen ion, and by the hydroxide ion
- Some undissociated acids and base may also produce a catalytic effect

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 Ionic Strength
- Increased ionic strength decreases the rate of reaction between oppositely charge ions and increase the rate reaction between similarly charged
ions
 Solvent
- Reaction of oppositely charge ions is increased by low dielectric solvents; Reaction of similarly charged ions is increased by high dielectric solvents

FACTORS AFFECTING DRUG STABILITY

 Hydrolysis (Solvolysis) -
- decomposition in aqueous solution is also pH dependent (ex. Ester hydrolysis, eg. Aspirin in aqueous sol’n, procain and atropine)
 Oxidation- reaction upon exposure to air or oxidizing chemicals or auto-oxidation (e.g. organic compounds: phenols, aromatic amines,
aldehydes , ethers, unsaturated aliphatic compounds ;
Pharmaceutical preparations: epinephrine, ascorbic acid, phenothiazines and vitamine A) .
 Photolysis – involves the degradation of drug by sunlight or daylight (photosensitivity)
Example: Riboflavin, Nifedipine and phenothiazine
 Racemization (isomerization and Epimerization) Example: protein mixtures, epinephrine and pilocarpine
Others:
 Different temperature
 Change in pH

METHODS OF PRODUCT STABILIZATION

 Selection of optimum or appropriate pH
 Addition of buffers
 Selection of proper solvent
 Addition of complexing agents such as bezocaine and/or caffeine complex
 Addition of Surfactants (nonionic and anionic retard hydroxide catalysis; cation increases hydroxide catalysis)
 Suspension formulation
 Refrigeration (exemption: Ampicillin Na : 4 hr stability in D5 water @ 50C= 10%decomposition; -200C 13% decomposition respectively)

Accelerated Stability Analysis

In the past it was the practice in many pharmaceutical manufacturing companies to evaluate the stability of pharmaceutical preparations by
observing them for a year or more. Corresponding to the normal time they would remain in stock and in use. Such method was time consuming. Thus,
accelerated studies at higher temperature were mostly employed by certain companies.
- it the method include testing the drug with an increase temperature, humidity and light
STRESS TESTING
A method used to elucidate the intrinsic stability of the drug substance as part of the product development strategy and is normally carried
out under more severe conditions than those used for accelerated testing.