Stability & Kinetics of Drugs UPDATED

Define drug stability.

The ability of a drug product to maintain chemical, physical, and microbiological integrity during storage and use.

What is chemical stability?

Drug retains chemical structure and potency within specified limits.

What is physical stability?

No change in appearance, taste, dissolution, or consistency.

What is microbiological stability?

Drug remains sterile or resistant to microbial growth.

List main mechanisms of drug decomposition.

Hydrolysis, oxidation, photolysis, and polymerization.

Define hydrolysis.

Decomposition of a molecule by reaction with water.

Functional groups prone to hydrolysis.

Esters, amides, lactams, imides, thiolesters.

Example of drug undergoing ester hydrolysis.

Aspirin or benzocaine.

Example of drug undergoing amide hydrolysis.

Penicillin or acetaminophen.

Effect of pH on hydrolysis rate.

Most drugs are most stable between pH 4–6.

How to protect a drug from hydrolysis.

Remove water, use nonaqueous solvents, refrigerate, adjust pH, use desiccants, or dry formulations.

Define oxidation.

Loss of electrons, usually with oxygen gain or hydrogen loss.

List drugs prone to oxidation.

Phenylephrine, steroids, antibiotics, vitamins, fats, and oils.

Describe oxidation by free radicals.

Initiation → propagation → termination chain reactions involving oxygen radicals.

How to protect from oxidation.

Exclude oxygen, use antioxidants, add chelators, store at low temperature, use amber containers, adjust pH.

List antioxidants for aqueous systems.

Ascorbic acid, sodium sulfite, sodium bisulfite, sodium thiosulfate.

List antioxidants for oil systems.

Ascorbyl palmitate, propyl gallate, α-tocopherol, BHA, BHT.

Role of chelating agents in oxidation prevention.

Bind heavy metals that catalyze oxidation; examples: EDTA, citric acid, tartaric acid.

Define photolysis.

Decomposition of drug molecules by light exposure.

List drugs affected by photolysis.

Hydrocortisone, prednisolone, riboflavin, ascorbic acid, folic acid.

How to protect from photodegradation.

Use amber glass or opaque containers; avoid UV exposure.

Define polymerization.

Two or more drug molecules combine to form complex, inactive products.

Example of polymerization.

Ampicillin forming dimers.

Define zero order kinetics.

Reaction rate is independent of drug concentration; rate = k₀.

Zero order half-life equation.

t½ = C₀ / (2k₀).

Define first order kinetics.

Reaction rate depends on concentration; rate = kC.

First order half-life equation.

t½ = 0.693 / k.

Define second order kinetics.

Reaction rate depends on the square of concentration; rate = kC².

Effect of temperature on reaction rate.

Increase of 10°C doubles or triples reaction rate.

Name the equation relating temperature and rate.

Arrhenius equation: k = Ae^(-Ea/RT).

Define accelerated stability testing.

Short-term study at high temperature and humidity to predict shelf-life.

Define long-term stability testing.

Study under recommended storage conditions for ≥12 months.

Purpose of Arrhenius plot.

Graph ln(k) vs 1/T to estimate rate constant and predict shelf-life.