Pharmaceutical Stability Quiz

Introduction to Drug Stability

• 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.

Drug Stability Data

• 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 Throughout Development

• 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.

Five Types of Drug Stability

• 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.

Why Stability is Important?

• 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.

Stability Studies

• 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.

Types of Changes in Drug Products

• 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.

Drug Stability and Stabilization Techniques

• 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.

1. Solid State 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).

Physical Changes/Instability

• 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.

Chemical Changes/Instability

• 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.

Chemical Degradation Study

• 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).

Elevated Temperature Studies

• 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.