SELF-EMULSIFYING DRUG DELIVERY SYSTEMS - FORMULATION AND BIOPHARMACEUTIC EVALUATION OF AN INVESTIGATIONAL LIPOPHILIC COMPOUND
SELF-EMULSIFYING DRUG DELIVERY SYSTEMS - FORMULATION AND BIOPHARMACEUTIC EVALUATION OF AN INVESTIGATIONAL LIPOPHILIC COMPOUND
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DOI：
10.1023/a:1018987928936
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发表时间：
1992-01-01
影响因子：
3.7
通讯作者：
POUTON, CW
中科院分区：
文献类型：
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作者：
CHARMAN, SA;CHARMAN, WN;POUTON, CW
自乳化药物递送系统（SEDDS）代表了亲脂性化合物传统口服制剂的可能替代品。 在本研究中，亲脂性化合物 WIN 54954 配制在中链甘油三酯油/非离子表面活性剂混合物中，该混合物在水介质中温和搅拌的条件下表现出自乳化作用。 使用激光衍射粒度仪研究乳化效率，以确定所得乳液的粒度分布。 优化配方由 25% (w/w) 表面活性剂、40% (w/w) 油和 35% (w/w) WIN 54954 组成，在 0.1 N HCl（37 摄氏度）中轻轻搅拌，快速乳化，产生平均液滴直径小于 3 μm 的分散体。 在平行交叉研究中，通过将自乳化制剂与聚乙二醇 600 (PEG 600) 溶液制剂作为预填充软明胶胶囊给予禁食的比格犬进行比较。 确定药代动力学参数，并通过与静脉注射比较来计算药物的绝对生物利用度。注射。 SEDDS 提高了血浆曲线在最大血浆浓度 (C(max)) 和达到最大浓度的时间 (t(max)) 方面的重现性。 WIN 54954 的绝对生物利用度与 SEDDS 或 PEG 制剂没有显着差异。
Self-emulsifying drug delivery systems (SEDDSs) represent a possible alternative to traditional oral formulations of lipophilic compounds. In the present study, a lipophilic compound, WIN 54954, was formulated in a medium chain triglyceride oil/nonionic surfactant mixture which exhibited self-emulsification under conditions of gentle agitation in an aqueous medium. The efficiency of emulsification was studied using a laser diffraction sizer to determine particle size distributions of the resultant emulsions. An optimized formulation which consisted of 25% (w/w) surfactant, 40% (w/w) oil, and 35% (w/w) WIN 54954 emulsified rapidly with gentle agitation in 0.1 N HCl (37-degrees-C), producing dispersions with mean droplet diameters of less than 3-mu-m. The self-emulsifying preparation was compared to a polyethylene glycol 600 (PEG 600) solution formulation by administering each as prefilled soft gelatin capsules to fasted beagle dogs in a parallel crossover study. Pharmacokinetic parameters were determined and the absolute bioavailability of the drug was calculated by comparison to an i.v. injection. The SEDDS improved the reproducibility of the plasma profile in terms of the maximum plasma concentration (C(max)) and the time to reach the maximum concentration (t(max)). There was no significant difference in the absolute bioavailability of WIN 54954 from either the SEDDS or the PEG formulations.