RESUMO
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.
Assuntos
Portadores de Fármacos , Emulsões , Nanopartículas , Ácido Oleanólico/farmacocinética , Preparações de Plantas/farmacocinética , Administração Oral , Animais , Disponibilidade Biológica , Química Farmacêutica , Formas de Dosagem , Composição de Medicamentos , Estabilidade de Medicamentos , Etilenoglicóis/química , Glicerídeos , Glicerol/análogos & derivados , Glicerol/química , Masculino , Microscopia Eletrônica de Transmissão , Óleos/química , Ácido Oleanólico/administração & dosagem , Ácido Oleanólico/sangue , Ácido Oleanólico/química , Compostos Orgânicos/química , Preparações de Plantas/administração & dosagem , Preparações de Plantas/sangue , Preparações de Plantas/química , Ratos , Ratos Sprague-Dawley , Solubilidade , Propriedades de Superfície , Tensoativos/química , Comprimidos , Tecnologia Farmacêutica/métodosRESUMO
Many pharmacokinetic studies of paclitaxel formulations with or without Cremophor (CrEL) have been performed on experimental animals. However, limited studies describe the different pharmacokinetic behaviors of paclitaxel in animals. The different distribution of drug in blood fractions may have great effect on its pharmacokinetic behaviors. Our present study was designed to study the characteristics of paclitaxel distribution in human, rabbit and rat blood, by measuring plasma-to-blood ratio (PBR) of paclitaxel in vitro and in vivo, and analyzing the results of equilibrium dialysis of paclitaxel with erythrocyte, plasma and hemoglobin. It was demonstrated that the paclitaxel PBR values in rat, unlike those in rabbit, are most significantly different from those in human, which may be due to distinct affinity of paclitaxel to blood fractions among different species. The effect of CrEL on increasing paclitaxel plasma concentration and in vitro & in vivo correlation in animal PBR values were observed. The findings in this study are of significance in the evaluation of the newly developed formulations of paclitaxel.
