Formulation and In Vivo Evaluation of Self-Nanoemulsifying Granules for Oral Delivery of a Combination of Ezetimibe and Simvastatin

Abstract

Self-nanoemulsifying granules were formulated with the objective of improving the bioavailability of the ezetimibe and simvastatin when administered together. Composition of self-nanoemulsifying system (SNS) was optimized using various modified oils, surfactant, and cosurfactant mixtures. SNSs were mixed with water and resultant emulsions were characterized for mean globule size and stability. SNSs were adsorbed on hydrophilic colloidal silicon dioxide to give free-flowing self-nanoemulsifying granules. Self-nanoemulsifying granules were characterized by X-ray diffraction pattern, scanning electron microscopy, dissolution profile, and for in vivo performance in hypercholesterolemic rats. X-ray diffraction studies and scanning electron microscopy indicated loss of crystallinity and/or solubilization of both drugs in the self-nanoemulsifying granules. Self-nanoemulsifying granules effected substantial increase in dissolution of the drugs as compared with pure powder of drugs. In vivo evaluation in rats showed significant decrease in the total cholesterol levels and triglyceride levels in rats as compared with positive control confirming potential of self-nanoemulsifying granules as a drug delivery system for the poorly water-soluble drugs.

Keywords:

• self-nanoemulsifying granules
• ezetimibe
• simvastatin
• colloidal silicon dioxide
• hyperlipidemia

ACKNOWLEDGEMENTS

The authors are thankful to Amrut Mody Research Foundation, Mumbai, India, for providing the financial support for this work. The authors thank Dr. B. M. Arora and (Mrs) Bhagyashree Chalke, Dept. of Solid State Physics, and Mr. Nilesh Kulkarni, Tata Institute of Fundamental Research (TIFR), Mumbai, India, for providing facility and assistance during scanning electron microscopy studies and X-ray diffraction studies. The authors are grateful to Dr. Evans Coutinho, Department of Chemistry and Molecular Modeling, Bombay College of Pharmacy, for providing facility and assistance to perform in silico studies of simvastatin.