Formulation of gastro-retentive floating tables of Diltiazem Hydrochloride wtih carnauba wax by melt granulation technique

Abstract

The study was carried out to investigate drug release profile of gastroretentive drug delivery system (GDDS) of diltiazem hydrochloride prepared with a hydrophilic polymer (hydroxylpropyl methyl cellulose), hydrophobic polymer (ethyl cellulose) and a waxy material (carnauba wax). Drug profiles were compared with a commercial formulation of the drug (MKT). Sodium bicarbonate (30%) was incorporated as gas generating agent. Formulations were either prepared alone with the individual polymer or admixed with carnauba wax. Formulations containing carnauba wax were prepared by melt granulation technique. Tablets were evaluated for tensile strength, in vitro buoyancy and drug release profiiles. Release data were subjected to analysis by four different mathematical models namely, – zero order flux, first order, Higuchi square root of time relationship and Korsmeyer equations. All formulated tablets and MKT had tensile strength values between 1.05 - 1.32 MNm^-2. One of the test formulations (F7) gave a comparable release profile with the commercial sample, MKT. For instance, the % maximum release (m∞) and time to attain this (t∞) for F7 and MKT were (96%, 99%) and (12, 12 h) respectively, while their dissolution rates (m∞/t∞) were 8 %h^-1 and 8.3 %h^-1 respectively. All the formulations fitted well into Korsmeyer and Peppas model (correlation coefficient r value ≥ 0.95). Release exponent (n) for F7 and MKT formulations were 0.150 and 0.286 respectively with a corresponding release rate constant values of 65.4 and 43.8. This showed that release of diltiazem hydrochloride from these formulations followed Fickian diffusion mechanism. An optimised GDDS of diltiazem hydrochloride using carnuba wax as a matrix, comparable with MKT has been developed.

Keywords: Gastroretentive drug delivery system, melt granulation, floating, diltiazem hydrochloride, Carnauba wax

Journal of Pharmaceutical and Allied Sciences, Vol. 7 No. 2 (2010)