Pharmaceutics and Dosage Form Design: Preformulation to Dissolution
Pharmaceutics and dosage form design covers preformulation, excipient selection, manufacturing, dissolution and stability - the practical core of formulation science, tested with descriptive and numerical items.
Core rules
- Preformulation: solubility, pKa, partition coefficient, polymorphism, hygroscopicity, flow (angle of repose, Carr's index, Hausner ratio) and compressibility.
- Dissolution models: Noyes–Whitney (rate proportional to surface area and solubility), zero-order, first-order, Higuchi (Q proportional to √t for matrix systems) and Hixson–Crowell (cube-root law for changing surface area).
- Tablet defects: capping and lamination (air entrapment, over-drying), picking and sticking (moisture, low-melting excipients), mottling (dye migration).
- ICH stability: long-term 25 °C/60% RH or 30 °C/65% RH for Zone IVb, and accelerated 40 °C/75% RH for six months; these data support shelf-life and storage statements.
Worked example
A 400 mg uncoated tablet is tested for uniformity of weight under the Indian Pharmacopoeia. The limit for tablets of 250 mg or more is ±5%, so the acceptable range is 380–420 mg. Not more than two tablets may fall outside this range, and no tablet may fall outside twice the limit (360–440 mg). A tablet weighing 375 mg is an outlier within the single-limit zone; three such tablets would fail the test.
Traps
Memorise the IP bands correctly (≤80 mg ±10%; >80 to <250 mg ±7.5%; ≥250 mg ±5%); do not use United States Pharmacopeia bands in an IP question; do not confuse Higuchi matrix release with zero-order reservoir release; and do not quote accelerated conditions without stating duration and purpose.