title: Formulation and in Vitro Evaluation of Self-microemulsifying Drug Delivery System Containing Fixed-Dose Combination of Atorvastatin and Ezetimibe.
abstract: This paper focuses on the development and physicochemical characterization of a self-microemulsifying drug delivery system (SMEDDS) containing a fixed-dose combination of atorvastatin (ATR) and ezetimibe (EZT). The solubility of both drugs was determined in excipient screening studies. Ternary-phase diagrams were drawn for 27 systems composed of different surfactants, cosurfactants, and oils at different surfactant-to-cosurfactant (S/CoS) ratios, and the system exhibiting the largest percentage area of the self-microemulsifying region was selected. The optimum oil ratio in the SMEDDS was selected by evaluating the mean droplet size of the resultant microemulsions. The underlying mechanism of the lower ATR loading capacity compared with EZT was elucidated by measurement of the zeta potential and UV absorption analysis. The results implied that ATR was located exclusively in the surfactant-cosurfactant layer, whereas EZT was located both in the microemulsion core and the surfactant-cosurfactant layer. In vitro dissolution studies showed that the SMEDDS had higher initial dissolution rates for both drugs when compared with marketed products. More importantly, EZT had a significantly increased dissolution profile in distilled water and pH 4.0 acetate buffer, implying enhanced bioavailability.
authors.affiliation: School of Pharmacy, Sungkyunkwan University.
authors.forename: Kyu-Mok
authors.initials: KM
authors.lastname: Hwang
authors.forename: Shin-Ae
authors.initials: SA
authors.lastname: Park
authors.forename: Ju-Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Chun-Woong
authors.initials: CW
authors.lastname: Park
authors.forename: Yun-Seok
authors.initials: YS
authors.lastname: Rhee
authors.forename: Eun-Seok
authors.initials: ES
authors.lastname: Park
mesh_terms: D000924:Anticholesteremic Agents / Q000008:administration & dosage* / Q000737:chemistry; D000069059:Atorvastatin / Q000008:administration & dosage* / Q000737:chemistry; D004338:Drug Combinations; D016503:Drug Delivery Systems; D045703:Emulsifying Agents / Q000737:chemistry*; D005079:Excipients / Q000737:chemistry*; D000069438:Ezetimibe / Q000008:administration & dosage* / Q000737:chemistry; D044367:Phase Transition; D012995:Solubility
chemical_list: D000924:Anticholesteremic Agents; D004338:Drug Combinations; D045703:Emulsifying Agents; D005079:Excipients; D000069059:Atorvastatin; D000069438:Ezetimibe