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Development and optimization of a self-microemulsifying drug delivery system for atorvastatin calcium by using D-optimal mixture design

Authors Yeom DW, Song YS, Kim SR, Lee SG, Kang MH, Lee S, Choi YW

Received 25 February 2015

Accepted for publication 16 April 2015

Published 5 June 2015 Volume 2015:10(1) Pages 3865—3878

DOI https://doi.org/10.2147/IJN.S83520

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Thomas J Webster

Dong Woo Yeom,1 Ye Seul Song,1 Sung Rae Kim,1 Sang Gon Lee,1 Min Hyung Kang,1 Sangkil Lee,2 Young Wook Choi1

1College of Pharmacy, Chung-Ang University, Seoul, 2College of Pharmacy, Keimyung University, Daegu, Republic of Korea

Abstract: In this study, we developed and optimized a self-microemulsifying drug delivery system (SMEDDS) formulation for improving the dissolution and oral absorption of atorvastatin calcium (ATV), a poorly water-soluble drug. Solubility and emulsification tests were performed to select a suitable combination of oil, surfactant, and cosurfactant. A d-optimal mixture design was used to optimize the concentration of components used in the SMEDDS formulation for achieving excellent physicochemical characteristics, such as small droplet size and high dissolution. The optimized ATV-loaded SMEDDS formulation containing 7.16% Capmul MCM (oil), 48.25% Tween 20 (surfactant), and 44.59% Tetraglycol (cosurfactant) significantly enhanced the dissolution rate of ATV in different types of medium, including simulated intestinal fluid, simulated gastric fluid, and distilled water, compared with ATV suspension. Good agreement was observed between predicted and experimental values for mean droplet size and percentage of the drug released in 15 minutes. Further, pharmacokinetic studies in rats showed that the optimized SMEDDS formulation considerably enhanced the oral absorption of ATV, with 3.4-fold and 4.3-fold increases in the area under the concentration-time curve and time taken to reach peak plasma concentration, respectively, when compared with the ATV suspension. Thus, we successfully developed an optimized ATV-loaded SMEDDS formulation by using the d-optimal mixture design, that could potentially be used for improving the oral absorption of poorly water-soluble drugs.

Keywords: atorvastatin, SMEDDS, d-optimal mixture design, optimization, dissolution, bioavailability
 

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