Higuchi's equation and beyond: overview of the formulation and application of a generalized model of drug release from polymeric matrices.

An account is presented of modeling and experimental work, which complements, in many useful ways, the excellent coverage, afforded by a recent dedicated issue edited by Siepmann and Peppas (Int. J. Pharm. 2011, 418(1)), of the theoretical background and many ramifications, as well as practical applications, of the Higuchi equation. The main notable feature of the said modeling work is formulation and successful practical application, of an ab initio generalized approach, based on solving the fundamental transport equations applicable to the operation of typical matrix-controlled release (MCR) devices. This approach (i) reduces to the Higuchi equation under the pertinent restrictive conditions but can duly handle most of its more complex ramifications and (ii) can be parameterized (by the use of appropriate data from the literature or from independent experiments) to adapt itself to the physics of the particular matrix-solvent-solute system under consideration; as demonstrated here with examples from our laboratory or from the literature. A distinctive feature of the experimental work is the extensive use of simpler "model" MCR systems, chosen so as to promote better understanding of the effect of various physicochemical parameters and mechanisms on drug MCR rate and kinetics. A concept of MCR device efficiency is also discussed.