William I. Higuchi

Bio: William I. Higuchi is an academic researcher from University of Utah. The author has contributed to research in topics: Dissolution & Iontophoresis. The author has an hindex of 61, co-authored 458 publications receiving 15971 citations. Previous affiliations of William I. Higuchi include University of California & University of Nebraska–Lincoln.

Release of medroxyprogesterone acetate from a silicone polymer.

Abstract: A study of the physicochemical factors involved in the in vitro release of medroxyprogesterone acetate (MPA) a water-insoluble steroid embedded in a silicone rubber matrix was based upon a model system which considered the matric boundary diffusion layer; extensive mathematical equations for the model are presented for planar and cylindrical cases. Initial and long-time release rates were obtained. Zones of MPA depletion were measured microscopically as a function of time and the partition coefficient of MPA was determined. Following relatively constant initial release rates a nonlinear dependence of release rates upon MPA concentration (3% 12% 24%) was found. As MPA diffused from the matrix well-defined zones of depletion developed and were photographed. Comparison of the present model to the T. Higuchi model of drug release (based on a purely matrix-controlled system) indicated that when boundary layer was considered a better fit of experimental data to theory was found. Findings suggest that the partition coefficient diffusion coefficients medroxyprogesterone acetate concentration within the polymer and agitation conditions play important roles in the release process. The applicability of the model to an in vivo system (in which slower release of MPA has been observed) is evaluated.

A Theoretical Basis for a Biopharmaceutic Drug Classification: The Correlation of in Vitro Drug Product Dissolution and in Vivo Bioavailability

Abstract: A biopharmaceutics drug classification scheme for correlating in vitro drug product dissolution and in vivo bioavailability is proposed based on recognizing that drug dissolution and gastrointestinal permeability are the fundamental parameters controlling rate and extent of drug absorption. This analysis uses a transport model and human permeability results for estimating in vivo drug absorption to illustrate the primary importance of solubility and permeability on drug absorption. The fundamental parameters which define oral drug absorption in humans resulting from this analysis are discussed and used as a basis for this classification scheme. These Biopharmaceutic Drug Classes are defined as: Case 1. High solubility-high permeability drugs, Case 2. Low solubility-high permeability drugs, Case 3. High solubility-low permeability drugs, and Case 4. Low solubility-low permeability drugs. Based on this classification scheme, suggestions are made for setting standards for in vitro drug dissolution testing methodology which will correlate with the in vivo process. This methodology must be based on the physiological and physical chemical properties controlling drug absorption. This analysis points out conditions under which no in vitro-in vivo correlation may be expected e.g. rapidly dissolving low permeability drugs. Furthermore, it is suggested for example that for very rapidly dissolving high solubility drugs, e.g. 85% dissolution in less than 15 minutes, a simple one point dissolution test, is all that may be needed to insure bioavailability. For slowly dissolving drugs a dissolution profile is required with multiple time points in systems which would include low pH, physiological pH, and surfactants and the in vitro conditions should mimic the in vivo processes. This classification scheme provides a basis for establishing in vitro-in vivo correlations and for estimating the absorption of drugs based on the fundamental dissolution and permeability properties of physiologic importance.

Membrane Technology and Applications

Abstract: Overview of membrane science and technology membrane transport theory membrane and modules concentration polarization reverse osmosis ultrafiltration microfiltration gas separation pervaporation ion exchange membrane processes - electrodialysis carrier facilitated transport medical applications of membranes other membranes processed.