Kale Amit A, Patravale Vandana B
Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Matunga, Mumbai 400019, India.
AAPS PharmSciTech. 2008;9(1):191-6. doi: 10.1208/s12249-008-9037-9. Epub 2008 Feb 5.
The ability of self-emulsifying drug delivery systems (SEDDS) to improve solubility, dissolution rate and bioavailability of a poorly water-soluble calcium channel blocker, nimodipine (NM) was evaluated in the present investigation. Solubility of NM in various oils, surfactants and cosurfactants was determined. The influence of the ratio of oil to surfactant + cosurfactant, pH of aqueous phase on mean globule size of resulting emulsions was studied by means of photon correlation spectroscopy. The NM loaded SEDDS selected for the in vitro and in vivo studies exhibited globule size less than 180 nm. In vitro dissolution studies indicated that NM loaded SEDDS could release complete amount of NM irrespective of the pH of the dissolution media. Pharmacokinetics of NM suspension, NM oily solution, NM micellar solution and NM SEDDS were evaluated and compared in rabbits. Relative bioavailability of NM in SEDDS was significantly higher than all the other formulations. NM loaded SEDDS were subjected to various conditions of storage as per ICH guidelines for 3 months. NM SEDDS successfully withstood the stability testing.
在本研究中,评估了自乳化药物递送系统(SEDDS)改善难溶性钙通道阻滞剂尼莫地平(NM)的溶解度、溶解速率和生物利用度的能力。测定了NM在各种油、表面活性剂和助表面活性剂中的溶解度。通过光子相关光谱法研究了油与表面活性剂+助表面活性剂的比例、水相pH对所得乳液平均粒径的影响。选择用于体外和体内研究的载NM SEDDS的粒径小于180nm。体外溶出研究表明,载NM SEDDS可释放出全部的NM,而与溶出介质的pH无关。在兔体内评估并比较了NM混悬液、NM油溶液、NM胶束溶液和NM SEDDS的药代动力学。NM在SEDDS中的相对生物利用度显著高于所有其他制剂。按照ICH指南,将载NM SEDDS在各种条件下储存3个月。NM SEDDS成功通过了稳定性测试。