油包水包水双重乳液:提高匹多莫德在大鼠体内口服生物利用度的优良递送系统。
Water-in-oil-in-water double emulsions: an excellent delivery system for improving the oral bioavailability of pidotimod in rats.
机构信息
Pharmaceutical Research Institute, China Pharmaceutical University, Nanjing, China.
出版信息
J Pharm Sci. 2011 Jun;100(6):2203-11. doi: 10.1002/jps.22443. Epub 2010 Dec 23.
The aims of this study were to prepare fine pidotimod-containing water-in-oil-in-water (W/O/W) double emulsions and to investigate the possibility of those emulsions as a delivery system for promoting the oral bioavailability of pidotimod. A modified two-step emulsification procedure was applied to prepare the double emulsions using medium-chain triglyceride as the oil phase, Tween 80 as the hydrophilic emulsifier, and Span 80 alone or in combination with different amount of phospholipids as the lipophilic emulsifiers. A fine W/O/W emulsion, with the encapsulation efficiency of 82 ± 3.4%, mean oil-droplet diameter of 3.93 ± 0.25 μm, and viscosity of 36.4 ± 0.93 mPa · s at 25 °C and 300 s(-1), was stable for 1 month at 4 °C. In addition, the oral bioavailability of pidotimod in rats, after intragastric administration of W/O/W double emulsions, was significantly higher than that of pidotimod control solution. Moreover, the maximum uptake time was significantly prolonged, suggesting an extra absorption pathway for W/O/W emulsions: a lymphatic circulation pathway. Those results demonstrated that W/O/W emulsions could become a potential formulation for improving the oral bioavailability of poorly absorbable drugs and suggested an important technology platform for the oral administration of peptide and peptidomimetic drugs.
本研究的目的是制备含有吡咯烷酮的精细水包油包水(W/O/W)双重乳液,并研究这些乳液作为促进吡咯烷酮口服生物利用度的给药系统的可能性。采用改良的两步乳化法,以中链甘油三酯为油相,吐温 80 为亲水性乳化剂,单独使用或与不同量的磷脂组合使用 Span 80 作为亲脂性乳化剂来制备双重乳液。W/O/W 乳液稳定性良好,可在 4°C 下稳定 1 个月,其包封效率为 82±3.4%,平均油滴直径为 3.93±0.25μm,在 25°C 和 300s(-1)时的粘度为 36.4±0.93mPa·s。此外,大鼠灌胃给予 W/O/W 双重乳液后,吡咯烷酮的口服生物利用度明显高于吡咯烷酮对照溶液。此外,最大摄取时间明显延长,提示 W/O/W 乳液具有额外的吸收途径:淋巴循环途径。这些结果表明,W/O/W 乳液可以成为提高难吸收药物口服生物利用度的潜在制剂,并为肽和拟肽药物的口服给药提供了重要的技术平台。