Drug stability

Stability

It can be defined as the ability of a particular formulation in a specific container or closure system to remain with in its physical, chemical, microbiological, therapeutic and toxicological specifications

Shelf Life

Refers to the duration of time during which a drug preparation will remain physically, chemically, therapeutically, toxicology, and microbiology stable (possessing NLT 90% of the labeled potency)

Expiration Date

It limits the period during which a preparation may be expected to have its labeled potency, provided the product has been stored as directed on the labeling

Significance of Accelerated Stability Studies

◉ To intensify the degradation loss with time

◉ To enable researchers to predict the shelf life of a product within a short period of time

◉ To determine the most stable formulation for a particular therapeutic actives (in preformulation studies)

Zone 1

Temperate

Zone 2

Subtropical

Zone 3

Hot and Dry

Zone 4

Hot and humid

Stress test (done on API)

○ This test is performed until the total physical and chemical degradation of the product is reached

○ This stability testing has a duration of 6-12 months

Transesterification

heat with alcohol and acid catalyst

Hydrolysis

heat with aq. acid or base (e.g. aq. H2SO4 or aq. NaOH) (see hydrolysis of esters for more details)

Amide preparation

heat with the amine, methyl or ethyl esters are the most reactive

Oxidation

involves the removal of an electropositive atom, radical or electron, or the addition of an electronegative atom or radical

Photodissociation

is a chemical reaction in which a chemical compound is broken down by photons.

Photolysis

is the degradation of drug molecules by normal sunlight or room light

Isomerization

This is the process of conversion of a drug into its optical or geometric isomers, which are often of lower therapeutic activity

Polymerization

The process by which two or more identical drug molecules combine together to form a complex molecule

Electrophoresis

This involves the movement of charged particle through a liquid under the influence of an applied potential difference

appearance

a pharmaceutical product is expected to look fresh, elegant and professional no matter how long it stands on the shelf

Uniformity

the manufacturers must ensure that the patient will receive the proper amount of the active ingredient in each dose

Availability

the active ingredient must be available to the patient throughout the expected shelf life of the preparation

Chemical Stability

causes chemical deterioration incompatibilities which may be

The most common degradation reactions that occur with small molecule drugs are

○ Solvolysis

○ Oxidation

○ Photolysis

○ Dehydration

○ Racemization

Factors Affecting Stability of a Pharmaceutical Product

◉ Stability of Active Ingredients

◉ Manufacturing process

◉ Container closure system

◉ Environmental conditions

◉ Storage

◉ Handling

Short Term / Accelerated Stability Studies

This involves the use of Exaggerated conditions of temperature, light, moisture, pH and humidity to test the stability of drug formulations

Important Parameters

◉ Drug Products

○ Loss of activity or potency of the active ingredient ○ Amount of degradation product

◉ Cosmetics

○ Retention of the physical qualities of freshly manufactured product

○ Instability that is gauged by its loss of elegance