An improved formulation screening and optimization method applied to the development of a self-microemulsifying drug delivery system.
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.
Liu
Ying
Y
Department of Pharmaceutics, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.
Chen
Zhi Qiang
ZQ
Zhang
Xin
X
Feng
Nian Ping
NP
Zhao
Ji Hui
JH
Wu
Shan
S
Tan
Rong
R
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
D000970:Antineoplastic Agents; D002018:Bufanolides; D004655:Emulsions; C022777:bufalin