Novel nanoemulsion for minimizing variations in bioavailability of ezetimibe

Abstract

The objectives of the present study were to develop an optimal nanoemulsion of ezetimibe and evaluate its stability, lipid lowering and pharmacokinetic potential. Solubility of ezetimibe was determined in various vehicles. Pseudoternary phase diagrams were constructed to determine the existence of nanoemulsion region. Formulations were selected from the oil/water nanoemulsion region and subjected to various thermodynamic stability and dispersibility tests. Release rate of optimized formulations was determined using in vitro dissolution test. The formulation used for evaluation contained Capryol 90 (10% v/v), Tween 80 (15% v/v), Transcutol^® P (30% v/v), double distilled water (45% v/v). The release of drug from the nanoemulsion was highly significant (P <0.001) when compared to the drug suspension. The value of total cholesterol in the group administered with the formulation TF1 was highly significant (P <0.001) with respect to the group administered with the suspension of the drug. The plasma concentration time profile of ezetimibe from nanoemulsion represented greater improvement of drug absorption than the marketed formulation and drug suspension. The shelf life of the nanoemulsion was found to be 5.94 years at room temperature. The present study established nanoemulsion to be a possible alternative for minimizing variation in bioavailability of ezetimibe.

Keywords::

• Nanoemulsion
• oral bioavailability
• ezetimibe
• pseudoternary phase diagram
• stability

Acknowledgments

The authors are thankful to Dr. Himanshu Bohidar of School of Physical Sciences, Jawaharlal Nehru University, New Delhi for his kind support in performing glouble size analysis and zeta potential determination in his lab. Ranbaxy Research Laboratory, Gurgaon, Haryana, India is thanked for carrying out in vivo analysis using LC/MS/MS in their Clinical Pharmacology and Pharamcokinetics department. A part of this research work has been presented as poster at the 1^st Nano Today Conference 2009, Biopolis, Singapore, 2–5 August 2009. The authors would also like to thank Mr. Pramod K. for improving the language of the manuscript.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.