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DrX Whiz Niraj
Unit 5: Drug Stability
Kinetics, Degradation & Shelf-Life
1. Introduction to Drug Stability
Drug stability is the ability of a pharmaceutical product to retain its Identity, Strength, Quality, Purity, and Safety throughout its shelf life.
Importance of Drug Stability:
Maintains therapeutic effect | Prevents toxicity | Determines shelf life | Helps decide proper storage conditions.Types of Instability: Chemical, Physical, Microbiological, Therapeutic, and Toxicological instability.
2. Reaction Kinetics & Order of Reaction
Reaction Kinetics is the study of the rate of chemical reactions and the factors affecting them.
Order of Reaction: The sum of the powers of the concentration terms involved in the rate equation.
Zero Order Reaction
Reaction in which the rate is independent of the concentration of reactants.
Unit of K₀: mol L⁻¹ sec⁻¹
Characteristics: Constant rate of reaction. Straight line obtained between Concentration (C) and Time (t). (Examples: Suspensions, Controlled release dosage forms).
First Order Reaction
Reaction in which the rate depends on the concentration of one reactant.
Unit of K₁: time⁻¹ (e.g., sec⁻¹)
Characteristics: Rate decreases with concentration. Straight line obtained between log Concentration and Time. Half-life remains constant. (Examples: Antibiotic degradation).
Pseudo Zero Order Reaction
A reaction which actually follows higher-order kinetics but behaves like zero order due to the excess concentration of one reactant (e.g., Suspensions where drug dissolves as it degrades).
3. Factors Influencing Degradation
1. Temperature (Arrhenius Equation)
Increase in temperature generally increases the rate of degradation (Rule of thumb: Rate doubles for every 10°C rise).
Where: K = Rate constant, A = Frequency factor, Ea = Activation energy, R = Gas constant, T = Absolute Temperature.
Other Factors:
- Solvent: Hydrolysis occurs faster in water.
- Ionic Strength & Dielectric Constant: Affects interactions between ionic drugs.
- Specific Acid-Base Catalysis: Reaction catalyzed specifically by H⁺ or OH⁻ ions.
4. Degradation Pathways & Prevention
| Degradation Pathway | Definition & Drugs Affected | Prevention Methods |
|---|---|---|
| 1. Hydrolysis | Decomposition by reaction with water. Drugs: Aspirin, Penicillin, Procaine. |
Use dry form, Non-aqueous solvents, Adjust pH, Moisture-proof containers. |
| 2. Oxidation | Loss of electrons or addition of oxygen. Drugs: Vitamin C, Adrenaline, Oils/Fats. |
Add Antioxidants (Ascorbic acid, BHT, BHA), Replace oxygen with Nitrogen gas. |
| 3. Photolysis | Decomposition of drugs due to UV/light. Drugs: Riboflavin, Nifedipine. |
Store in Amber colored or opaque containers, Store in dark. |
5. Accelerated Stability Testing
Definition: Storage of a product under exaggerated conditions (High temperature, High humidity) to predict its shelf life rapidly.
Key Terms to Remember:
- Shelf Life (t₉₀): Time during which the product retains at least 90% of its original potency.
- Expiration Dating: The date placed on the container after which the product should not be used.
t₉₀ = 0.105 / K
Half-Life (First Order):
t₁/₂ = 0.693 / K
6. Solve & Score (Important Numericals)
Numerical 1: First Order Rate Constant
Problem: The half-life of a drug is 6 hours. Calculate the rate constant.
Formula: K = 0.693 / t₁/₂
Solution:
K = 0.693 / 6
K = 0.1155 hr⁻¹
Numerical 2: Shelf Life Calculation
Problem: The rate constant of a drug is 0.002 day⁻¹. Calculate its shelf life.
Formula: t₉₀ = 0.105 / K
Solution:
t₉₀ = 0.105 / 0.002
t₉₀ = 52.5 days
🔥 Exam Corner: Must Read Questions
- 2 Marks: Define Zero and First order reaction, Shelf life (t90), Arrhenius equation.
- 5 Marks: Explain Hydrolysis and Oxidation with prevention methods. Solve the t90 numerical.
- 10 Marks: Discuss Accelerated Stability Testing and Expiration dating in detail using the Arrhenius plot.