Development and optimization of a self-microemulsifying drug delivery system for atorvastatin calcium by using D-optimal mixture designopen access
- Authors
- Yeom, Dong Woo; Song, Ye Seul; Kim, Sung Rae; Lee, Sang Gon; Kang, Min Hyung; Lee, Sangkil; Choi, Young Wook
- Issue Date
- Jun-2015
- Publisher
- DOVE MEDICAL PRESS LTD
- Keywords
- atorvastatin; SMEDDS; D-optimal mixture design; optimization; dissolution; bioavailability
- Citation
- INTERNATIONAL JOURNAL OF NANOMEDICINE, v.10, pp 3865 - 3878
- Pages
- 14
- Journal Title
- INTERNATIONAL JOURNAL OF NANOMEDICINE
- Volume
- 10
- Start Page
- 3865
- End Page
- 3878
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/11387
- DOI
- 10.2147/IJN.S83520
- ISSN
- 1178-2013
1178-2013
- 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.
- Files in This Item
-
- Appears in
Collections - College of Pharmacy > School of Pharmacy > 1. Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.