Department of Pharmaceutics, Roland Institute of Pharmaceutical Sciences, Berhampur, Orissa, India.
Colloids Surf B Biointerfaces. 2013 Jan 1;101:414-23. doi: 10.1016/j.colsurfb.2012.06.031. Epub 2012 Jul 16.
The current work aims to prepare the solid self-nanoemulsifying granules (SSNEGs) of ondansetron hydrochloride (ONH) to enhance its oral bioavailability by improving its aqueous solubility and facilitating its absorption though lymphatic pathways. Preformulation studies including screening of excipients for solubility and pseudoternary phase diagrams suggested the suitability of Capmul MCM as lipid, Labrasol as surfactant, and Tween 20 as cosurfactant for preparation of self-emulsifying formulations. Preliminary composition of the SNEDDS formulations were selected from the phase diagrams and subjected to thermodynamic stability studies and dispersibility tests. The prepared liquid SNEDDS formulations were characterized for viscosity, refractive index, droplet size and zeta potential. The TEM study confirmed the formation of nanoemulsion following dilution of liquid SNEDDS. The optimized liquid SNEDDS were transformed into free flowing granules by adsorption on the porous carriers like Sylysia (350, 550, and 730) and Neusilin™ US2. Solid state characterization employing the FTIR, DSC and powder XRD studies indicated lack of any significant interaction of drug with the lipidic and emulsifying excipients, and porous carriers. In vitro drug release studies indicated faster solubilization of the drug by optimized SSNEGs (over 80% within 30 min) vis-à-vis the pure drug (only 35% within 30 min). In vivo pharmacokinetic studies in Wistar rats observed significant increase in C(max) (3.01-fold) and AUC (5.34-fold) using SSNEGs compared to pure drug, whereas no significant difference (p>0.1) was observed with the liquid SNEDDS. Thus, the present studies ratify the bioavailability enhancement potential of SSNEGs of ONH prepared using porous carriers.
本工作旨在制备盐酸昂丹司琼（ONH）的固体自微乳给药系统颗粒（SSNEGs），以提高其口服生物利用度，方法是提高其水溶解度并通过淋巴途径促进其吸收。包括对溶解度和伪三元相图进行辅料筛选的预配方研究表明，Capmul MCM 适合作为脂质，Labrasol 作为表面活性剂，Tween 20 作为助表面活性剂，以制备自乳化制剂。从相图中选择 SNEDDS 制剂的初步组成，并进行热力学稳定性研究和分散性测试。对制备的液体 SNEDDS 制剂进行粘度、折射率、粒径和 Zeta 电位的测定。TEM 研究证实了液体 SNEDDS 稀释后纳米乳的形成。将优化的液体 SNEDDS 吸附在多孔载体（如 Sylysia（350、550 和 730）和 Neusilin™ US2）上，转化为自由流动的颗粒。采用 FTIR、DSC 和粉末 XRD 研究进行固态特征化，表明药物与脂质和乳化辅料以及多孔载体之间不存在任何显著的相互作用。体外药物释放研究表明，优化的 SSNEGs （在 30 分钟内超过 80％）比纯药物（在 30 分钟内仅 35％）更快地使药物溶解。在 Wistar 大鼠中的体内药代动力学研究表明，与纯药物相比，SSNEGs 使 Cmax（增加 3.01 倍）和 AUC（增加 5.34 倍）显著增加，而液体 SNEDDS 则没有观察到显著差异（p>0.1）。因此，本研究证实了使用多孔载体制备的 ONH 的 SSNEGs 的生物利用度增强潜力。
