Effect of Channeling Agents on Release Kinetics of Stavudine from Methocel K100 LVCR and Ethocel 20 cps Based Matrix Tablets

Abstract

The study was performed to investigate the effect of channeling agent on the release profile of
Stavudine from Methocel K100 LVCR and Ethocel 20 cps based matrix systems. Stavudine, a nucleoside analog
drug, is used in the treatment of acquired immune deficiency syndrome (AIDS). Stavudine matrix tablet was prepared
using Methocel K100 LVCR and Ethocel 20 cps as polymer and also using PEG 3350 and PEG 6000 as channeling
agents. The drug release mechanisms from different matrix tablets were explored and explained by zero order, first
order, Higuchi, Korsmeyer and Hixson-Crowell equations. The release rate, extent and mechanisms were found to be
governed by polymer type used and the content of the channeling agent. It was found that the release of drug from the
matrix tablet was increased with the increasing concentration of channeling agent. However, PEG 6000 enhanced the
release of drug greater than PEG 3350 from the matrix. On the other hand, Stavudine matrix containing Ethocel 20
cps showed a strong tendency to retard the drug release to 51-56% after 8 hours of dissolution, whereas the release
was found to be increased for the Methocel containing matrix to 90-100%. Kinetic modeling of dissolution profiles
revealed drug release mechanism ranged from diffusion controlled or Fickian transport to anomalous type or non-
Fickian transport, which was mainly dependent on the presence of relative amount of channeling agent and type of
polymer. These studies indicate that the proper balance between a matrix forming agent and a channeling agent can
produce optimum drug dissolution kinetics from Stavudine matrix tablet. The mechanism was also revealed by
Scanning Electron Microscope (SEM) pictures taken at various intervals of dissolution which showed that the extent
of pore formation in the matrix increases with the increasing amount of channeling agent and also the hydrophilic
nature of the polymer used in the formulation.