School of Pharmacy, University of Otago, Dunedin, New Zealand.
J Pharm Sci. 2012 May;101(5):1721-31. doi: 10.1002/jps.23054. Epub 2012 Jan 31.
The influence of lipid composition and drug load on the in vitro performance of lipid-based drug delivery systems was investigated during dispersion and in vitro lipolysis of two self-nanoemulsifying drug delivery systems (SNEDDS). SNEDDS preconcentrates consisted of the same mass ratios of lipid, surfactant, and cosolvent but varied in the chain length of the lipid component. Utilization of the surfactant Cremophor EL resulted in pronounced changes in the droplet size of dispersed SNEDDS containing increasing drug loads of the poorly water-soluble compound simvastatin (SIM). In contrast, the droplet size of dispersed medium-chain (MC)-SNEDDS based on the surfactant Cremophor RH40 was not affected by increasing drug loads of SIM, whereas the droplet size of the corresponding long-chain (LC)-SNEDDS increased. During 60 min in vitro lipolysis, MC-SNEDDS maintained approximately 95% of SIM in solution, independent of the drug load. At the start of lipolysis of LC-SNEDDS, up to 34% of the drug precipitated. However, the initial precipitate dissolved in the lipolysis medium 30 min after start of in vitro lipolysis. The study suggests that drug load and lipid composition should be considered for the design of SNEDDS. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:1721-1731, 2012.
研究了两种自微乳药物传递系统（SNEDDS）在分散和体外脂肪酶解过程中，脂质组成和药物载量对基于脂质的药物传递系统的体外性能的影响。SNEDDS 预浓缩物由相同质量比的脂质、表面活性剂和共溶剂组成，但脂质成分的链长不同。表面活性剂 Cremophor EL 的使用导致含有不同药物载量的疏水性差的化合物辛伐他汀（SIM）的分散 SNEDDS 的液滴尺寸发生明显变化。相比之下，基于表面活性剂 Cremophor RH40 的中链（MC）-SNEDDS 的液滴尺寸不受 SIM 药物载量增加的影响，而相应的长链（LC）-SNEDDS 的液滴尺寸增加。在 60 分钟的体外脂肪酶解过程中，MC-SNEDDS 保持约 95%的 SIM 溶解在溶液中，与药物载量无关。在 LC-SNEDDS 的脂肪酶解开始时，高达 34%的药物沉淀。然而，初始沉淀物在体外脂肪酶解开始 30 分钟后溶解在脂肪酶解介质中。该研究表明，在设计 SNEDDS 时应考虑药物载量和脂质组成。© 2012 年 Wiley 期刊出版公司和美国药剂师协会 J Pharm Sci 101:1721-1731, 2012。
