Multiple-layer, direct-compression, controlled-release system: in vitro and in vivo evaluation.

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.