Pharmaceutical Sciences: Medicinal Chemistry, Pharmaceutics and Biopharmaceutics
From molecule to dosage form
This domain spans medicinal chemistry, pharmaceutics, biopharmaceutics and analysis. In medicinal chemistry, know how functional-group ionization (pKa) governs solubility and permeability, how salt formation alters dissolution rate, and how prodrugs bypass absorption or stability limits. In pharmaceutics, be able to assign excipient roles - diluent, binder, disintegrant, lubricant, glidant, coating - and to distinguish immediate-, delayed- and extended-release mechanisms (osmotic pump, matrix, reservoir, ion exchange).
The numbers that matter
Bioavailability (F) is the fraction of an administered dose reaching systemic circulation unchanged. Bioequivalence compares rate and extent of absorption - AUC, Cmax, Tmax - between two products, typically using 80–125% confidence intervals for AUC and Cmax. Dissolution is often rate-limiting for BCS class II drugs (low solubility, high permeability). Stability follows kinetics: first-order degradation has t90 = 0.105/k, while zero-order degradation depletes a constant amount per unit time. Sterile compounding requires attention to isotonicity, pH compatibility, and preservative-free formulations where the route demands it.
Traps
Treating bioavailability and bioequivalence as synonyms; expecting a generic to match the brand's Cmax exactly rather than falling within accepted limits; forgetting that a prodrug is designed to have low parent-drug bioavailability at the absorption site; and confusing t90 (time for 10% loss) with half-life (50% loss).
Worked example
A weak acid has pKa 4.4. At plasma pH 7.4, Henderson–Hasselbalch gives log([A⁻]/[HA]) = 7.4 − 4.4 = 3, so the ionized-to-unionized ratio is about 1000:1. That predicts high aqueous solubility, poor lipid diffusion across membranes and minimal renal tubular reabsorption - exactly the reasoning a question expects when it asks where such a drug distributes or how it is eliminated.