title: Development and optimization of a self-microemulsifying drug delivery system for atorvastatin calcium by using D-optimal mixture design.
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.
authors.affiliation: College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea.
authors.forename: Dong Woo
authors.initials: DW
authors.lastname: Yeom
authors.affiliation: College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea.
authors.forename: Ye Seul
authors.initials: YS
authors.lastname: Song
authors.affiliation: College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea.
authors.forename: Sung Rae
authors.initials: SR
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea.
authors.forename: Sang Gon
authors.initials: SG
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea.
authors.forename: Min Hyung
authors.initials: MH
authors.lastname: Kang
authors.affiliation: College of Pharmacy, Keimyung University, Daegu, Republic of Korea.
authors.forename: Sangkil
authors.initials: S
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea.
authors.forename: Young Wook
authors.initials: YW
authors.lastname: Choi
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000069059:Atorvastatin / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D001682:Biological Availability; D016503:Drug Delivery Systems; D004655:Emulsions; D008297:Male; D008954:Models, Biological; D011092:Polyethylene Glycols / Q000737:chemistry; D011136:Polysorbates / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry
chemical_list: D004655:Emulsions; D011136:Polysorbates; D013501:Surface-Active Agents; D011092:Polyethylene Glycols; D000069059:Atorvastatin; C018557:glycofurol
keywords: SMEDDS; atorvastatin; bioavailability; d-optimal mixture design; dissolution; optimization