Design and Optimization of a Multiparticulate Gastroretentive Dosage Form For Better Control Of Gastric Acidity

The concept of multiunit gastroretentive microspheres can be utilized to provide a more reliable and long lasting release of drug in the stomach for local and systemic action. The floating microspheres beneficially alter the absorption of drug, thereby enhancing bioavailability. Famotidine, being a poorly bioavailable drug due toreasons unrelated to hepatic metabolism, is ideally suited to be delivered through a controlled release floating multiunit dosage form for slow release in the stomach and subsequent complete absorption in the intestine. In the present study, non aqueous solvent evaporation technique was employed to develop polymethylmethacrylate (PMMA) microspheres of famotidine. All formulation development trials leading to the successful batches have been disclosed. They were characterized physic-chemically including in vitro floating and drug release studies. Microspheres followed either zero-order or higuchi kinetics in drug release. They were floating for > 8 hours in simulated gastric juice. A 5-component simplex mixture design was followed to simulate the blend of microspheres required to optimize the drug release profile as per the pharmacokinetic need. Statistical optimization helped in achieving the desired target release by predicting the optimum blend to be 9:12:79 %w/w of microspheres having drug-polymer ratios (1:1):(1:2):(1:2.5) respectively, which was validatedexperimentally. A high similarity factor of 77% was achieved with the drug release from developed blend of microspheres in comparison to the target release profile. Hence, a statistically designed formulationdevelopment study could optimize the product in short time with minimal wastage of resources.