Development of self nanoemulsifying drug delivery systems for the enhancement of oral bioavailability of lipophilic drugs

Abstract

Low bioavailability of lipophilic drugs remains a challenge in the treatment of all diseases. The objective of this research work was to formulate and characterize self-nanoemulsifying drug delivery systems (SNEDDS) containing Lacidipine (LCDP), Raloxifene Hydrochloride (RLFH) and Raloxifene Base (RLFB) to improve the oral bioavailability. Formulations were evaluated for solubility, self emulsification time, transparency, thermodynamic stability, cloud point, globule size, surface morphology, drug content, in-vitro dissolution, ex-vivo permeation, stability, oral bioavailability and lymphatic drug transport. In the development of LCDP SNEDDS, Captex 810D, Tocopherol Glycerol Succinate (TPGS), Tween-60, Transcutol P and Polyethylene Glycol (PEG) 400 was selected based on the solubility study. LCDP SNEDDS was prepared by simple mixing method and characterized for its in-vitro and invivo performance. In-vitro dissolution of SNEDDS showed more than 80 % newlineof drug release within 15 min. The ex-vivo permeation of LCDP from SNEDDS is 4.8- and 9-fold higher compared to LCDP suspension in the absence and presence of verapamil (P-gp and CYP inhibitor) respectively. The stability study of the SNEDDS confirmed no environmental effect on the physical nature and drug content. Oral bioavailability of LCDP with SNEDDS is 2.5 times higher compared to marketed tablet. newline newline newline