Prepration and in vitro Evaluation of bilayered floating tablets of isosorbide dinitrates

Abstract

Background: Isosorbide di-nitrate (ISD) is used as a vasodilator in patients with angina pectoris. Recently, efforts have been made to reach a long retention time in the upper part of the gastrointestinal tract using floating bi-layer systems. Objective: This study was performed to design bilayer floating tablets of ISD to give immediate release and sustained release. Bilayer floating tablets comprised two layers, i.e immediate release and controlled release layers. Method: Bilayer floating systems of ISD were prepared using hydroxypropylmethyl cellulose (HPMC K4M), polyvinyl pyrolidone (PVP K 30), and microcrystaline cellulose, which may increase the residence time in the gastrointestinal tract. Direct compression method was used for this formulation. The immediate release layer is comprised sodium starch glycolate as a superdisintegrant, the sustained release layer is comprised HPMC K4M as the release retarding polymer and microcrystalin cellulose as diluent. Sodium bicarbonate was used as a gas generating agent.This tablets were evaluated for hardness, friability, weight variation, drug content, floating properties and in vitro release pattern. Results:. The optimized formulation (I1+C9) was found to be buoyant for 8 h in stomach. The results of release showed that I1 formulation and ISD® tablet ( immediate release) had 82.77% and 96.92% drug release after 5 min, respectively (p>o.o5). C9 formulation and ISD tablet® (controlled release) showed 82.47% and 81.34%, drug release after 2 hours, respectively (p>o.o5). The drug release in the bi-layer floating tablet was found to be 30.73%, 89.46% and 99.81% within 5 minutes, 2 and 8 hours, respectively. Polyvinyl pyrrolidone and ethyl cellulose sustained the release of ISD from the controlled release layer for more than 8 hours in the stomach. Conclusion: Optimum tablet may improve the bioavailability of the drug by increasing patient compliance, reducing the frequency of drug use and prolonging the presence time of the drug in the stomach.