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Current Drug Delivery

Editor-in-Chief

ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

Research Article

Optimization of Performance Variables of Exemestane Nanosuspension Using Box-Behnken Design to Improve Dissolution and Oral Bioavailability

Author(s): Komal Parmar* and Jay Shah

Volume 18, Issue 8, 2021

Published on: 12 January, 2021

Page: [1160 - 1173] Pages: 14

DOI: 10.2174/1567201818999210112190716

Price: $65

Abstract

Aim: Present investigation was aimed to fabricate nanocrystal of exemestane, an anticancer drug with poor dissolution properties and oral bioavailability.

Methods: Influence of various process parameters on the formulation of exemestane nanosuspension using media milling technique were investigated in the trial batches. Box-Behnken design was applied with independent variables identified in the preliminary studies, viz. X1-Milling time, X2-Amount of stabilizer and X3-Amount of milling agent. In vitro dissolution and in vivo studies were carried out. Solid state characterization (PXRD, SEM, and DSC) studies demonstrated physical changes in drug due to nano-crystallization. Accelerated stability studies of optimized formulation were carried out.

Results: Individual process attributes exhibited a significant effect on the average particle size of exemestane nanosuspension. Dissolution studies revealed enhancement in drug release rate as compared to pure exemestane powder. The in vivo pharmacokinetic parameters of exemestane nanosuspension showed significant improvement in Cmax and AUC0-t, about 283.85% and 271.63%, respectively suggesting amelioration in oral bioavailability by 2.7-fold as compared to pure exemestane. Accelerated stability studies of the optimized formulation suggested stability of the nanocrystals for at least a six-month period.

Conclusion: Nanocrystals prepared by media milling technique were successful in improving the poor dissolution properties and oral bioavailability of exemestane.

Keywords: Exemestane, nanosuspension, nanocrystals, dissolution, oral bioavailability, box-behnken design.

Graphical Abstract

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