Charman S A, Charman W N, Rogge M C, Wilson T D, Dutko F J, Pouton C W
Sterling Research Group, Rensselaer, New York 12144.
Pharm Res. 1992 Jan;9(1):87-93. doi: 10.1023/a:1018987928936.
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 microns. 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 (Cmax) and the time to reach the maximum concentration (tmax). There was no significant difference in the absolute bioavailability of WIN 54954 from either the SEDDS or the PEG formulations.
自乳化药物递送系统（SEDDSs）是亲脂性化合物传统口服制剂的一种可能替代方案。在本研究中，一种亲脂性化合物WIN 54954被制成中链甘油三酯油/非离子表面活性剂混合物，该混合物在水介质中温和搅拌条件下呈现自乳化现象。使用激光衍射粒度仪研究乳化效率，以确定所得乳液的粒径分布。一种优化配方由25%（w/w）表面活性剂、40%（w/w）油和35%（w/w）WIN 54954组成，在0.1 N盐酸（37℃）中温和搅拌下迅速乳化，产生平均液滴直径小于3微米的分散体。通过在平行交叉研究中给禁食的比格犬口服预填充软胶囊形式的自乳化制剂和聚乙二醇600（PEG 600）溶液制剂进行比较。测定药代动力学参数，并通过与静脉注射比较计算药物的绝对生物利用度。SEDDS在最大血浆浓度（Cmax）和达到最大浓度的时间（tmax）方面提高了血浆曲线的重现性。WIN 54954从SEDDS或PEG制剂中的绝对生物利用度没有显著差异。
