title: Comparison of bile salt/phosphatidylcholine mixed micelles in solubilization to sterols and stability.
abstract: Androst-3β,5α,6β-triol (Triol) is a promising neuroprotective agent, but its poor solubility restricts its development into parenteral preparations. In this study, Triol is significantly solubilized by bile salt/phosphatidylcholine mixed micelles (BS/PC-MM). All BS/PC-MM systems are tested to remarkably improve the drug solubility with various stabilities after drug loading. Among them, the sodium glycocholate (SGC)/egg phosphatidylcholine (EPC) system with 2:1 ratio in weight and the total concentration of SGC and EPC of 100 mg/mL is proved to produce stable mixed micelles with high drug loading. It is found that the stability of drug-loaded mixed micelles is quite different, which might be related to the change in critical micelle concentration (CMC) after incorporating drugs. SGC/EPC and SGC/soya phosphatidylcholine (SPC) remain transparent under accelerated conditions and manifest a decreased CMC (dropping from 0.105 to 0.056 mg/mL and from 0.067 to 0.024 mg/mL, respectively). In contrast, swine bile acid-sodium salt (SBA-Na)/PC and sodium deoxycholate (SDC)/PC are accompanied by drug precipitation and reached the maximum CMC on the first and the third days, respectively. Interestingly, the variation of CMC under accelerated testing conditions highly matches the drug-precipitating event in the primary stability experiment. In brief, the bile salt/phosphatidylcholine system exists as a potential strategy of improving sterol drug solubility. CMC variation under accelerated testing conditions might be a simple and easy method to predict the stability of drug-loaded mixed micelles.
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University.
authors.forename: Qin
authors.initials: Q
authors.lastname: Guo
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University; Guangzhou First People's Hospital, Guangzhou Medical University.
authors.forename: Jie
authors.initials: J
authors.lastname: Cai
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University.
authors.forename: Pengyu
authors.initials: P
authors.lastname: Li
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University.
authors.forename: Dongling
authors.initials: D
authors.lastname: Xu
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Ni
authors.affiliation: Guangzhou Cellprotek Pharmaceutical Co., Ltd., Science Park, Guangzhou, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wen
authors.affiliation: Guangzhou Cellprotek Pharmaceutical Co., Ltd., Science Park, Guangzhou, People's Republic of China.
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
authors.affiliation: Guangzhou Cellprotek Pharmaceutical Co., Ltd., Science Park, Guangzhou, People's Republic of China.
authors.forename: Suizhen
authors.initials: S
authors.lastname: Lin
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Hu
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000737:chemistry*; D004355:Drug Stability; D008823:Micelles; D010713:Phosphatidylcholines / Q000737:chemistry* / Q000494:pharmacology*; D012995:Solubility; D013261:Sterols / Q000737:chemistry* / Q000494:pharmacology*; D013552:Swine
chemical_list: D001647:Bile Acids and Salts; D008823:Micelles; D010713:Phosphatidylcholines; D013261:Sterols
keywords: bile salt/phosphatidylcholine; mixed micelles; solubilizing; stability; sterols