Self-nano-emulsifying drug delivery systems of Atorvastatin Calcium Liquid Filled in Hard Shell Capsules for Improved Oral Bioavailability in Rabbits

Abstract

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. 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. In the present study a Self-nano-emulsifying drug delivery systems (SNEDDS) was developed and formulated as a Liquid filled in hard shell capsule to improve the bioavailability of ATR. 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. From the study, it was concluded that the bioavailability of ATR was enhanced by formulating ATR as Liquid SNEDDS filled in hard shell capsules.