DEVELOPMENT OF ISOSORBIDE-5-MONONITRATE SUSTAINED RELEASE MATRIX TABLET BY STATISTICAL OPTIMIZATION TECHNIQUE

Abstract

The aim of the project is to prepare and optimize the sustained release matrix tablets of Isosorbide-5-mononitrate (ISMN).
Elimination half-life of ISMN is 4-5 h and has to be administered 2-3 times a day. In order to reduce the dosage frequency
and to increase patient compliance sustain release preparation was made. The tablets were formulated by wet granulation
technique using HPMCK4M, Eudragit NE30D, and Ethylcellulose polymers. The constrained mixture experimental design
was used to prepare systematic model formulations, which were composed of thee formulation variables: the content of
HPMCK4M, Eudragit NE30D, and Ethylcellulose. Prepared tablets were evaluated for hardness, friability, % drug content.
Drug release was evaluated in phosphate buffer pH-6.8 and the drug release responses were evaluated at 1 h, 2 h, 4 h, and 6
h. The result shows that the HPMC is a major release-retarding polymer. Result of optimized formula coincided well with
the predicted value, indicating it was quite useful for optimizing pharmaceutical formulation. The analysis of the release
profiles in the light of distinct kinetic models (zero-order, first-order, Higuchi, Peppas) shows that the value of release
exponent n for all formulation ranging from 0.4633-0.7184, which indicate that the mechanism of release is anomalous
diffusion. This is due to the coupling of diffusion and relaxation.