The Formulation and Evaluation of Gastro-Bilayer Floating Tablets of Losartan Potassium as Immediate Release Layer and Ramipril Hydrochloride as Sustained Release Floating Layer

摘要

Objectives: A sustained release Gastro-bilayer floating tablets with reduced dosing frequency and increased drug bioavailability is developed. The dosage form is suitable for the release of two drugs simultaneously in a single dosage unit i.e. Losartan Potassium and Ramipril Hydrochloride. The SeDeM system for selection of powder blend for direct compression gave the parameter index value of ≥0.5 which is considered as best in terms of compression properties. The prepared dosage form provided sustained effect of the drug for 12 hr by Non-Fickian, controlled diffusion and swollen matrix. Peppa’s release model is best suited for the final formulation of batches. Optimized formulation exhibited floating time of 12 hr and floating lag time of less than 1 min. In-vitro dissolution studies shows 96% of the both the drugs release. The swelling and erosion of polymers is studied by Scanning Electron Microscopy. The data obtained from Analysis of variance demonstrated the significance of the model with a P-value of less than 0.05. Methods: SeDeM system was adopted on powder blend before direct compression for preparation of tablet, the hydroxyl propyl methyl cellulose was used as a rate-controlling polymer and a mixture of citric acid and Sodium bicarbonate formed the floating layer. Results: Radius values through SeDeM diagram was plotted and index values are calculated and resulted in an index value of ≥0.5. The pre-compression and post compressional parameters are as per Indian Pharmacopeia specifications. The best formulation for gastric bilayer tablet had a combination of Hydroxy propyl methyl cellulose K15M and Sodium Carboxy methyl cellulose which gave 99.57% drug dissolution within 12 hr. Conclusion: Gastro-Bilayer Floating Tablets of Losartan as Immediate Release layer and Ramipril as sustained-release floating layer are successfully developed. The problem of poor solubility of drugs can be solved by optimization of blend through SeDeM expert System. Hydroxy propyl methyl cellulose K15M, K4M and Carbopol 934 are helpful in achieving the sustained effect of the drug for 12 hr by Non-Fickian, controlled diffusion and swollen matrix. Peppa’s release model is best suited for the final formulation batches based on the drug release mechanisms.