Pharmaceutics: Dosage Form Design, Biopharmaceutics and Stability
The Pharmaceutics domain in GPAT tests how a drug substance becomes a stable, effective dosage form: unit operations, formulation, biopharmaceutics and stability. Questions often combine a numerical calculation with a formulation principle.
Formulation and quality control
- Tablets are evaluated for weight variation (IP limits tighten from ±10% at ≤80 mg to ±5% above 250 mg), hardness (generally 4–10 kg/cm²), friability (<1% w/w after 100 revolutions) and disintegration.
- BCS Class I: high solubility/high permeability; Class II: low solubility/high permeability (dissolution-rate limited); Class III: high solubility/low permeability (permeability limited); Class IV: low/low.
- Noyes–Whitney: dissolution rate increases with surface area and solubility, and decreases with diffusion-layer thickness.
Stability
Accelerated testing is commonly 40°C ± 2°C/75% RH ± 5% for six months; Arrhenius treatment links degradation rate to temperature, and Q10 approximates a 2–3-fold rate rise per 10°C.
Worked example
A batch of 100,000 tablets is labelled 200 mg API; a 3% manufacturing overage is used and the raw API assays 98.0%. API required = 200 mg × 100,000 × 1.03 = 20,600,000 mg = 20.6 kg. Correcting for assay: 20.6/0.98 = 21.02 kg. The overage is applied to the API, not the total tablet weight.
Marks-losing traps
Applying overage to tablet weight; quoting friability after 4 minutes instead of 100 revolutions; calling Class II permeability-limited; mixing accelerated and long-term storage conditions.