Self-nano-emulsifying Drug Delivery Systems of Atorvastatin Calcium Liquid Filled in Hard Shell Capsules for Improved Oral Bioavailability in Rabbits

Abstract

Aims and Objectives: Atorvastatin calcium (ATR) is a BCS class II drug showing poor bioavailability due to limited aqueous solubility. In the present study, a self-nano-emulsifying drug delivery system (SNEDDS) was developed and formulated as a liquid filled in a hard shell capsule to improve the bioavailability of ATR. Methods: Different oils were screened through the saturated stability method, and the amount of ATR solubilized in the respective oils was analysed through HPLC at 245nm. A ternary phase diagram was plotted to obtain the optimized ratio of oil, surfactant, and co-surfactant to formulate SNEDDS. The prepared ATR SNEDDS was filled into hard shell capsules, band sealed, and subjected to various evaluations like disintegration time, self-emulsification time, precipitation time assessment, globule size analysis and zeta potential. Then the in vitro dissolution studies were carried out. The optimized SNEDDS formulation was filled in a hard shell capsule, and in vivo studies were performed on rabbits to compare the pharmacokinetic parameters with the marketed formulation and pure ATR. Results: Capmul MCM as the oil component showed five-fold solubility of ATR and was selected for the preparation of ATR-SNEDDS. The SNEDDS formulation showed an entrapment efficiency of 89.76±4.1% ATR with a globule size of 385±1.9 nm and an emulsification time of 5 seconds. It was established from the study that liquid ATR-SNEDDS had relative bioavailability enhanced by 1.7 times in comparison to the marketed formulations (Lipvas) and 4.8 times with respect to pure ATR. Conclusion: From the study, it was concluded that the bioavailability of ATR was enhanced by formulating ATR as Liquid SNEDDS filled in hard shell capsules.