title: An improved formulation screening and optimization method applied to the development of a self-microemulsifying drug delivery system.
abstract: This study focused on the development of an improved formulation screening and optimization method for a self-microemulsifying drug delivery system (SMEDDS). Solubility study and construction of a ternary phase diagram were carried out to determine the primary formulation components. Experimental design combined with a desirability study was employed to obtain the optimal formulation composition. The obtained bufalin SMEDDS formulation was Maisine 35-1 and Miglyol 812N (1 : 1, w/w) of 29.5%, Cremophor EL of 39.5%, and Transcutol P of 30.5%. It showed desired properties with droplet size of 33.9 nm; polydispersity index of 0.126; equilibrium solubility of 12.6 mg/ml, and 73.6% of soluble drug post-digestion. A rapid release of up to 21% occurred in the first 10 min. A bufalin SMEDDS was well absorbed at all intestinal segments. The absorption of bufalin from a SMEDDS was 2.38-fold higher than that of bufalin suspension in terms of relative bioavailability. The studies on solubility and ternary phase diagrams combined with experimental design may offer a valuable and efficient strategy for developing and optimizing a SMEDDS to obtain optimal formulations with desired characteristics.
authors.affiliation: Department of Pharmaceutics, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Zhi Qiang
authors.initials: ZQ
authors.lastname: Chen
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Nian Ping
authors.initials: NP
authors.lastname: Feng
authors.forename: Ji Hui
authors.initials: JH
authors.lastname: Zhao
authors.forename: Shan
authors.initials: S
authors.lastname: Wu
authors.forename: Rong
authors.initials: R
authors.lastname: Tan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002018:Bufanolides / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems / Q000379:methods*; D004655:Emulsions / Q000737:chemistry*; D007408:Intestinal Absorption; D008297:Male; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility
chemical_list: D000970:Antineoplastic Agents; D002018:Bufanolides; D004655:Emulsions; C022777:bufalin