FORMULATION AND EVALUATION OF TABLET PREPARED BY COAMORPHOUS SYSTEM CONTAINING ANTI-HYPERTENSIVE AND ANTI-HYPERLIPIDEMIC DRUG
Objective: Amlodipine besylate (AML) and Atorvastatin calcium (ATR) belong to biopharmaceutical classification system (BCS) class II (i.e. low solubility and high permeability) which leads to variable bioavailability. Hence, the aim of this study was to enhance the solubility of both drugs by utilizing the co-amorphous technique. This converted form and physical mixture of both drugs were utilized in the formulation of tablets.
Methods: The co-amorphous system was prepared by using rotary flash evaporator. Solubility study was carried out to investigate the dissolution advantage of prepared co-amorphous form. Total twelve formulations were formulated by keeping constant drugs concentrations utilizing direct compression technique among which F1 to F6 contains co-amorphous AML-ATR (Co-A AML-ATR) and F7 to F12 contains a physical mixture of AML and ATR as active pharmaceutical ingredient (APIs). Pre-compression and post-compression studies were carried out to all twelve formulations. Stability study was performed to the optimized formulations as per ICH guidelines.
Results: Mixture obtained after evaporation was found to become amorphous. FTIR study shows no evidence of intermolecular interactions between AML and ATR. The solubility of both AML and ATR were increased in almost one fold as compared to their respective crystalline counterparts. Pre-compression parameters of all twelve formulations blend fall under excellent to fair to flow properties. Post-compression parameters of all twelve formulations were within the specifications. But in vitro drug release of formulations F5, F6, F11, and F12 showed % drug release as per IP. Stability study of optimized formulations was observed with, no significant difference in % drug release.Conclusion: The co-amorphous system can be prepared by utilizing rotary flash evaporator and the same was confirmed by XRPD and FTIR studies. The dissolution rate of the co-amorphous system was greater than that of the crystalline counterpart. Based on the results; F5 and F6 are considered as optimized formulations. Optimized formulations were stable during the stability study.
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