Formulation development and bioavailability evaluation of a self-nanoemulsified drug delivery system of oleanolic acid.
This study aims to formulate and evaluate bioavailability of a self-nanoemulsified drug delivery system (SNEDDS) of a poorly water-soluble herbal active component oleanolic acid (OA) for oral delivery. Solubility of OA under different systems was determined for excipient selection purpose. Four formulations, where OA was fixed at the concentration of 20 mg/g, were prepared utilizing Sefsol 218 as oil phase, Cremophor EL and Labrasol as primary surfactants, and Transcutol P as cosurfactant. Pseudo-ternary phase diagrams were constructed to identify self-emulsification regions for the rational design of SNEDDS formulations. Sefsol 218 was found to provide the highest solubility among all medium-chained oils screened. Efficient self-emulsification was observed for the systems composing of Cremophor EL and Labrasol. The surfactant to cosurfactant ratio greatly affected the droplet size of the nanoemulsion. Based on the outcomes in dissolution profiles, stability data, and particle size profiles, three optimized formulations were selected: Sefsol 218/Cremophor EL/Labrasol (50:25:25, w/w), Sefsol 218/Cremophor EL/Labrasol/Transcutol P (50:20:20:10, w/w), and Sefsol 218/Cremophor EL/Labrasol/Transcutol P (50:17.5:17.5:15, w/w). Based on the conventional dissolution method, a remarkable increase in dissolution was observed for the SNEDDS when compared with the commercial tablet. The oral absorption of OA from SNEDDS showed a 2.4-fold increase in relative bioavailability compared with that of the tablet (p < 0.05), and an increased mean retention time of OA in rat plasma was also observed compared with that of the tablet (p < 0.01). These results suggest the potential use of SNEDDS to improve dissolution and oral bioavailability for poorly water-soluble triterpenoids such as OA.
Xi
Jia
J
Institute of Chinese Medical Sciences, University of Macau, Av. Padre Tomás Pereira, S.J. Taipa, Macau SAR, China.
Chang
Qi
Q
Chan
Chak K
CK
Meng
Zhao Yu
ZY
Wang
Geng Nan
GN
Sun
Jia Bei
JB
Wang
Yi Tao
YT
Tong
Henry H Y
HH
Zheng
Ying
Y
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D004304:Dosage Forms; D004337:Drug Carriers; D004339:Drug Compounding; D004355:Drug Stability; D004655:Emulsions; D005026:Ethylene Glycols / Q000737:chemistry; D005989:Glycerides; D005990:Glycerol / Q000031:analogs & derivatives / Q000737:chemistry; D008297:Male; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles; D009821:Oils / Q000737:chemistry; D009828:Oleanolic Acid / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D009930:Organic Chemicals / Q000737:chemistry; D028321:Plant Preparations / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013499:Surface Properties; D013501:Surface-Active Agents / Q000737:chemistry; D013607:Tablets; D013678:Technology, Pharmaceutical / Q000379:methods
D004304:Dosage Forms; D004337:Drug Carriers; D004655:Emulsions; D005026:Ethylene Glycols; D005989:Glycerides; D009821:Oils; D009930:Organic Chemicals; D028321:Plant Preparations; D013501:Surface-Active Agents; D013607:Tablets; C440220:Labrasol; C000515:cremophor EL; D009828:Oleanolic Acid; C010111:carbitol; D005990:Glycerol