Pharmaceutics and Dosage Form Design: From Properties to Performance
This domain covers preformulation, dosage-form selection and the quality tests that show a design works. Exam questions connect physicochemical properties to excipients, manufacturing route and performance.
Design logic
- Preformulation: solubility, pKa, partition coefficient, polymorphism, hygroscopicity, particle size, flow, compressibility and excipient compatibility.
- BCS: Class I high solubility/high permeability; II low solubility/high permeability; III high solubility/low permeability; IV low/low. Class II often needs dissolution enhancement; Class III may need permeation enhancement or modified release.
- Common systems: tablets (direct compression or wet granulation), capsules, suspensions, emulsions, semisolids, sterile products and modified-release forms.
Quality control tests
- Tablets: weight variation, hardness, friability, disintegration, dissolution and content uniformity.
- Suspensions: sedimentation, redispersibility and particle size; emulsions: globule size and phase separation.
- Sterile products: sterility, pyrogen/endotoxin, particulate matter and container integrity.
Worked example
A weak-acid BCS Class II drug has solubility 0.02 mg/mL at pH 1.2 and 2 mg/mL at pH 6.8. Reasoning: gastric solubility is poor, so a conventional immediate-release tablet may fail dissolution. Options include a salt form, micronisation, solid dispersion or lipid formulation; test dissolution in biorelevant media at pH 1.2 and 6.8; confirm no excipient incompatibility. Do not assume the higher intestinal solubility solves the gastric dissolution step.
Traps
Confusing hardness with dissolution; treating friability and crushing strength as the same; choosing modified release for a drug with poor colonic absorption; ignoring polymorphism; using a single dissolution time point when the acceptance table requires staged testing.