Formulation design, absorption mechanism and bioavailability of nanoemulsions for enhancing oral absorption of raloxifene
10.16438/j.0513-4870.2018-0514
- VernacularTitle:促进雷洛昔芬口服吸收的纳米乳处方设计、吸收机制及生物利用度研究
- Author:
Chuan-li HUANG
1
;
Yong-qiu WU
2
;
Bei HUANG
2
;
Jian-feng YANG
2
;
Jun-han WAN
1
;
Cai-feng ZHANG
1
;
Xiao-ying LONG
2
Author Information
1. School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China
2. School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China
- Publication Type:ORIGINAL ARTICLES
- Keywords:
raloxifene;
nanoemulsion;
formulation design;
transcellular cell migration;
bioavailability
- From:
Acta Pharmaceutica Sinica
2018;53(10):1726-1735
- CountryChina
- Language:Chinese
-
Abstract:
Oral formulations of nanoemulsions (NE) were systematically designed, and then their effects on oral absorption of raloxifene (RAL), including their absorption mechanisms were investigated. RAL solubility in water and various excipients of NE and oil-water partition coefficient[P(O/W)] of RAL were examined. Next the optimal compatibility between emulsifiers and oils in NE were ascertained by emulsification ability. Proportions of each component and optimal RAL-NE were fully confirmed by a pseudo-ternary phase diagram and drug loading, respectively. RAL-NE quality was evaluated by particle size, zeta potential, morphology, entrapment efficiency and stability in simulated gastrointestinal fluid. A MDCK cell model was used to study the in vitro transport mechanism of RAL-NE. Oral bioavailability of RAL-NE was eventually performed in SD rats. RAL can be classified as BCSⅡ based on the solubility and P(O/W). The best formulation of RAL-NE was composed of linoleic acid (LOA):isopropyl palmitate (IPP):cremophor RH40 (RH40):alcohol as 1.67:3.33:3:2. Drug loading in pre-nanoemulsion was 15 mg·g-1 andentrapment efficiency of RAL in NE was (79.4 ±0.4)%. The particle size, zeta potential and drug content of RAL-NE were maintained in the simulated gastrointestinal fluid. The in vitro transport mechanism of RAL-NE in MDCK cells was mainly clathrin-mediated endocytosis. The oral bioavailability of RAL in RAL-NE relative to RAL-suspension was 171.9%. The best formulation of RAL-NE studied systematically was confirmed to significantly improve the RAL absorption by in vitro and in vivo evaluations (P < 0.05). This paper provides references for oral NE research and development.
