Preparation of a matrix type multiple-unit gastro retentive floating drug delivery system for captopril based on gas formation technique: in vitro evaluation

Abstract

A gastro retentive floating drug delivery system with multiple-unit minitab's based on gas formation technique was developed in order to prolong the gastric residence time and to increase the overall bioavailability of the drug. The system consists of the drug-containing core units prepared by direct compression process, which are coated with three successive layers of an inner seal coat, effervescent layer (sodium bicarbonate) and an outer gas-entrapped polymeric membrane of an polymethacrylates (Eudragit RL30D, RS30D, and combinations of them). Only the system using Eudragit RL30D and combination of them as a gas-entrapped polymeric membrane could float. The time to float decreased as amount of the effervescent agent increased and coating level of gas-entrapped polymeric membrane decreased. The optimum system floated completely within 3 min and maintained the buoyancy over a period of 12 h. The drug release was controlled and linear with the square root of time. Increasing coating level of gas-entrapped polymeric membrane decreased the drug release. Both the rapid floating and the controlled release properties were achieved in the multiple-unit floating drug delivery system developed in this present study. The analysis of the parameter dissolution data after storage at 40 degrees C and 75% RH for 3 months showed, no significant change indicating the two dissolution profiles were considered to be similar (f2 value is more than 50).

Fig. 1

Design of minitablets with different coating layers

Fig. 2

DSC thermograms of captopril, excipients and their combinations

Fig. 3

SEM of a core units, b effervescent layered units and c complete final coated units

Fig. 4

Effect of effervescent layer level on floating lag time

Fig. 5

Effect of polymer coatings on floating lag time at a 12% of effervescent coating levels

Fig. 6

Cumulative percentage of drug released with different polymer coating levels

Fig. 7

Dissolution profiles after storage at 40 °C and 75% RH for 3 months [batch: Eudragit RS:RL30D (1:3) 5% coating]