Pharmaceutical Stability Quiz

Study Notes

Drug stability is defined as the ability of a drug formulation to remain within its physical, chemical, microbiological, and toxicological limits.
USP defines drug stability as the extent to which a product retains its properties during storage and use.

Stability data comes from data on the drug in its commercial packaging.
Stability data includes selected parameters that together form the stability profile.
Pharmaceutical products need to maintain their quality, purity, and strength throughout their stated storage period and conditions.

Drug stability is investigated throughout the development process.
Drug substance stability is initially assessed in the preformulation stage.
Pharmacists at this stage will determine drug substance compatibility with various solvents, solutions, and excipients for formulation development.
Optimizing formulation is based on preformulation data and continues through formulation development.
After regulatory approval, pharmacists need to understand proper storage and handling.

Chemical Stability: Each active ingredient retains its chemical integrity and labelled potency.
Physical Stability: Original physical properties like appearance, palatability, uniformity, and dissolution remain.
Microbiological Stability: Sterility and resistance to microbial growth are maintained as per specifications. Antimicrobial agents retain effectiveness.
Therapeutic Stability: The therapeutic effect remains unchanged.
Toxicological Stability: No significant increase in toxicity.

Evidence on drug quality changes over time due to environmental factors like temperature, humidity, and light.
Establish a re-test period and recommended storage conditions.
Changes in physical, chemical, or microbiological properties can affect drug efficacy and safety.

Drug Substances (DS): The unformulated drug substance, in conjunction with excipients, forms dosage forms.
Drug Products (DP): The final dosage form in its packaged state ensuring appropriate drug substance changes are within acceptable levels.

Physical Changes: Appearance, Melting point, Clarity/color of solutions, moisture content, Crystalline modification (polymorphs), Particle size.
Chemical Changes: Increase in degradation rate, decrease in assay.
Microbial Changes: Microbial growth or degradation.

Ideal shelf life for commercial pharmaceutical products is 3 years, with 90-95% drug potency maintained.
Designing solid dosage forms requires understanding of inherent stability of drug substance and excipients, as well as the formulation process.
For drug substances, three areas of stability are assessed; solid-state stability, compatibility studies (drug+excipients), and solution-phase stability.

Includes both physical and chemical stability.
Physical changes include polymorphic transitions and hygroscopicity.
Chemical changes include reactions like solvolysis, oxidation, photolysis, and pyrolysis.
Examination of chemical structure can expose vulnerability to degradation (e.g., presence of unsaturation).

Factors like solubility, pKa, melting point, crystal form, and equilibrium moisture content can affect physical stability.
Amorphous materials are less stable than their crystalline counterparts.
Relatively dense materials are often more stable.

Solid-state reactions are generally slow. Stress conditions are often used to investigate stability and the data extrapolated to predict stability under normal conditions.
High temperatures can remove moisture and render the sample apparently stable but can expose it to other reactions.

Hydrolysis: Occurs in drugs like esters, amides, and lactams.
Oxidation/Reduction: Loss or gain of electrons. Affects vitamins, tetracyclines, and morphine.
Photolysis: Reactions caused by light exposure, impacting vitamins, riboflavin, and folic acid.
Isomerization: Conversion to a less effective form (e.g., levo vs. dextro forms).

Stability tests are often done at elevated temperatures (40-60°C) along with ambient humidity.
Samples are kept at higher temperatures to observe chemical and physical changes at regular intervals.
No change after 30 days at 60°C suggests excellent stability prognosis.
Arrhenius treatment can be used to calculate degradation rates at lower temperatures.