ISBN : 978-93-85073-24-3 drug lipophilicity, particle size, viscosity of the medium, solubilization by native surfactants and co-ingested foodstuffs and pka in relation to the GI pH profile [123]. The mechanism and kinetics of drug release are dependent on the solubility of the active moiety and the swelling and erosion properties of the polymer, with water soluble drugs being released predominantly by diffusion with a limited contribution from matrix erosion and anomalous diffusion resulting from the relaxation of the macromolecular polymer chains [124]. The release of water soluble moieties will typically follow first order release kinetics. Water insoluble drugs are released predominantly through matrix erosion and therefore exhibit time independent or zeroorder release kinetics [125-130]. The Biopharmaceutics Classification System In the past decade, a greater understanding of the molecular transport in relation to physico-chemical properties especially solubility has led to the evolution of a biopharmaceutics classification system (BCS), which is becoming a road map governing future drug design, development and delivery. The BCS sets the criteria for allowing a drug substance, in an immediate release form to circumvent a bioequivalence study. It classifies the drugs into four major categories (Table 1.2) according to two main parameters; the solubility and permeability behaviours of each molecule [131-132]. Table 1.2: Biopharmaceutics Classification System (BCS) of drug molecules Biopharmaceutics Classification System I High solubility – High permeabilitya II Low solubility – High permeabilityb III High solubility – Low permeabilityc IV Low solubility – Low permeabilityd a. Exhibit dissolution rate-limited absorption (generally very well absorbed). b. Exhibit solubility rate-limited absorption. c. Exhibit permeability rate-limited absorption. d. Exhibit both, solubility and permeability rate-limited absorption with very poor oral bioavailability. 11
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