Development of Sustained Release Preparations of Metoclopramide Hydrochloride Based on Fatty Matrix

Abstract

Sustained release formulations of metoclopramide HCl (4-amino-5-chloro-N-(2-diethylaminoethyl)-2-
methoxybenzamide hydrochloride) (MH) were prepared using carnauba wax (CW) and stearic acid (SA) as matrix
formers. Granules were prepared by melt granulation method while direct compression technique was used to prepare
the tablets. The drug release profiles of these products were studied by in-vitro dissolution testing in simulated
gastric, gastrointestinal and intestinal media of pH 1.2, 4.5 and 7.5, respectively. The increase in the proportion of SA
in the granules produced a concomitant decrease of the initial drug release rate but later on the release rate was
enhanced in the intestinal medium. Drug release was found to be affected by compression force and stirring rate but
also showed a dependency on pH of the dissolution fluid. The fastest release rate was found at pH 4.5 and the slowest
at pH 1.2 which was consistent with the drug’s solubility behavior. Matrix erosion and water uptake rates were
highest in the intestinal medium and lowest in the gastric medium. The drug release kinetics followed the Higuchi’s
model in all cases.