Preparation And Evaluation Of A Gas Formation-based Multiple-Unit Gastro-Retentive Floating Delivery System Of Dipyridamole
The aim of this study was to prepare mini tablets to be filled into a capsule that is designed to float on the gastric contents based on gas formation technique. The drug-containing core mini-tablets were prepared by wet granulation method followed by a coating of the core units with seal coating, an effervescent layer and a gas-entrapping polymeric membrane (Eudragit RS30D, RL30D). Dipyridamole, which is predominantly absorbed in the upper part of GI tract and unabsorbed/insoluble at the lower intestine, was used as a model drug. The effect of the preparative parameters like amount of the effervescent agent layered onto the seal coated units, type and coating level of the gas-entrapping polymeric membrane, floating ability and drug release properties of the multiple-unit FDDS were evaluated. The formulations were evaluated for pharmacopoeial quality control tests. Physical parameters were found to be within the acceptable limits. The system using Eudragit® RL30D as a gas-entrapping polymeric membrane exhibited floating properties. The time to float decreased as amount of the effervescent agent increased and coating level of gas-entrapping polymeric membrane decreased. The optimum system exhibited complete floating within 3 minutes and maintained that buoyancy over a period of 8 hours. The drug release was sustained and linear with the square root of time. Increasing the coating level of the gas-entrapping polymeric membrane decreased drug release. Both the rapid-floating and sustained-release properties were achieved in the multiple-unit floating delivery system developed in this study. The in vivo gastric residence time was examined by radiograms and it was found that the units remained in the stomach for about 6 hours. The analysis of the dissolution data after storage at 40°C and 75% RH for 6 months showed no significant change indicating good stability.