Effect of Formulation Variables of Gastroretentive Floating Tablets of an Anti-Hypertensive agent using different Grades of Hydrophillic Polymers

摘要

Losartan potassium (LP) is an orally active non-peptide angiotensin -II receptor antagonist, used in the treatment of hypertension and have narrow therapeutic index, short biological half-life (l-2h), poor bio availability (25-35%), Due to these reasons conventional tablets should administer 3-4 times per day to maintain plasma drug concentrations within the therapeutic window. To overcome these drawbacks, sustained release gastro retentive floating tablets were prepared to enhance the patient compliance. Floating tablets were prepared with different grades of Hypromellose polymers along with Sodium bicarbonate, citric acid and characterized (Pre and post compression parameters) to optimize the best formulation. Lubricated blend was characterized for angle of repose, bulk density, tapped density and compressibility index. Compressed tablets were characterized for Hardness, friability, assay, related substances, in vitro drug release, etc. Based on the results, it was concluded that LFT10 formulation prepared with combination of Metolose 90SH-4000SR and Metolose 90SH-100000SR was optimized as best formulation. In vitro dissolution data of best formulation fitted in different mathematical models like zero, first orders, Higuchi, Hixon Crowell and Korsmeyer Peppas models and found that the drug release following zero order, non fickian diffusion mechanism. The optimized formulation (LFT10) also exposed to accelerated stability condition (40°C/ 75%RH) and found satisfactory as per ICH guidelines.