title: Multiple-layer, direct-compression, controlled-release system: in vitro and in vivo evaluation.
abstract: A new approach to achieve controlled drug delivery is demonstrated for a triple-layer tablet, which simultaneously combines the principles of diffusion and dissolution. Heckel's equation was used to characterize the compression behavior of formulation components. A balanced proportion of each component and a model drug (theophylline) were selected to avoid lamination after ejection and ensure coherent compaction. In vitro release profiles over a period of 10 h in different dissolution media and hydrodynamic conditions were similar and resulted in an n value of 0.786, signifying anomalous release kinetics. The n value is calculated from a curve fit to the empirical equation: Mt/Minfinity = Ktn, where Mt and Minfinity denote the amount of drug released at time t and at infinite time, respectively, K denotes the proportionality constant, and n characterizes the type of release mechanism operative during the dissolution process. In vivo study in human subjects after administration of the experimental triple-layer system exhibited a steady rise in plasma concentration up to 7 h. The actual amount of drug absorbed by the body was calculated by the Wagner-Nelson technique, and a linear relationship was observed between the percentage absorbed in vivo and the percentage dissolved in vitro. The proposed triple-layer model appears to provide good correlation between in vitro and in vivo results with maximum flexibility with respect of dose, duration range, and ease of production.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Temple University, Philadelphia, PA 19140.
authors.forename: R A
authors.initials: RA
authors.lastname: Fassihi
authors.forename: W A
authors.initials: WA
authors.lastname: Ritschel
mesh_terms: D000328:Adult; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004058:Diffusion; D004339:Drug Compounding; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D012995:Solubility; D013500:Surface Tension; D013607:Tablets; D013806:Theophylline / Q000008:administration & dosage / Q000493:pharmacokinetics
chemical_list: D003692:Delayed-Action Preparations; D013607:Tablets; D013806:Theophylline