Oral Drug Delivery and Bioavailability
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Lesson 1 of 9
Notes
Oral Bioavailability
Bioavailability (F) is the fraction of an administered dose that reaches the systemic circulation in an unchanged, pharmacologically active form. For an intravenous dose, F = 100% by definition. Oral bioavailability is reduced by incomplete absorption (dissolution, solubility, permeability barriers) and first-pass metabolism (intestinal wall and hepatic CYP450 metabolism before systemic circulation). F = fraction absorbed × (1 − first-pass extraction). For highly extracted drugs (e.g. lidocaine, propranolol), hepatic extraction ratio >60% severely limits oral bioavailability.
Solid Dosage Forms
Tablets are the most common oral dosage form. Tablet manufacture involves: active pharmaceutical ingredient (API) + excipients → granulation (wet or dry) → compression → film coating. Excipients serve critical functions: binders (hold tablet together — microcrystalline cellulose, PVP), disintegrants (facilitate tablet breakup on contact with water — croscarmellose sodium, sodium starch glycolate), lubricants (prevent sticking to punches — magnesium stearate), fillers/diluents (add bulk — lactose, calcium phosphate), glidants (improve powder flow — colloidal silica).
Disintegration leads to dissolution, which leads to absorption. The rate-limiting step for Class II BCS drugs is dissolution. Dissolution testing (USP apparatus 1 and 2) is a quality control tool simulating in vivo conditions.
Modified Release Formulations
Modified release (MR) formulations alter the timing or rate of drug release to improve efficacy, reduce adverse effects, or improve adherence. Types: (1) Delayed release (enteric-coated) — polymer coating resistant to gastric acid, dissolves at intestinal pH ≥6 (e.g. omeprazole, enteric aspirin to protect gastric mucosa); (2) Extended release (ER/XR/SR) — matrix tablets (hydrophilic HPMC swells to control drug release), reservoir systems (rate-controlling membrane, e.g. nifedipine GITS), osmotic systems (OROS — osmotic pressure drives drug out through a laser-drilled hole, e.g. oxybutynin); (3) Immediate release (IR) — rapid dissolution intended.