Department of Pharmacy, China Pharmaceutical University, Nanjing, PR China.
Drug Dev Ind Pharm. 2013 May;39(5):724-32. doi: 10.3109/03639045.2012.689766. Epub 2012 May 27.
In this study, a self-emulsifying pellet (SEP) was prepared in order to improve the bioavailability of bifendate (DDB). First, a liquid self-emulsifying drug delivery system (SEDDS) was formulated, and then further developed into the SEP by extrusion/spheronization technology using the reconstituted emulsion as the adhesive. The optimized liquid SEDDS consisted of Miglycol(®) 840, a mixture of Cremorphor(®) EL and Solutol HS(®) 15 (1:2, w/w), and Transcutol HP as the oil phase, the surfactant and the co-surfactant at a weight ratio of 40:45:15 (w/w/w), respectively. The SEP were prepared using a mixture of MCC, lactose, and mannitol (45:45:10, w/w/w) as solid adsorbents. The SEP with 40% (w/w) of the liquid SEDDS was round-shaped with a uniform size (800-1000 µm). There was no difference in droplet size between the emulsions obtained from the liquid SEDDS or the SEP (169.8 ± 6.3 nm and 163.7 ± 3.8 nm). Compared with that of DDB pills (less than 20%), in vitro release of DDB from the SEP (over 80% within 60 min) was significantly enhanced in 0.1N HCl, although slower than that of the liquid SEDDS (over 80% within 5 min). AUC of DDB of the SEP after oral administration in rats exhibited 2.36-fold greater than that of DDB pills and no significant difference compared with that of the liquid SEDDS. In conclusion, our studies illustrated that extrusion/spheronization technique could be a useful method to prepare this SEP and it could be a promising way for enhancing oral bioavailability of poorly water-soluble drugs.
在这项研究中，制备了自乳化微丸（SEP），以提高双丁酚（DDB）的生物利用度。首先，制备了液体自乳化药物传递系统（SEDDS），然后通过挤出/球形化技术进一步将其开发成 SEP，使用再构成乳液作为粘合剂。优化的液体 SEDDS 由 Miglycol®840、Cremophor®EL 和 Solutol HS®15（1:2，w/w）的混合物以及 Transcutol HP 作为油相、表面活性剂和助表面活性剂组成，重量比分别为 40:45:15（w/w/w）。SEP 是使用 MCC、乳糖和甘露醇（45:45:10，w/w/w）的混合物作为固体吸附剂制备的。含有 40%（w/w）液体 SEDDS 的 SEP 呈圆形，粒径均匀（800-1000 µm）。从液体 SEDDS 或 SEP 获得的乳液的粒径没有差异（169.8 ± 6.3nm 和 163.7 ± 3.8nm）。与 DDB 丸（不到 20%）相比，DDB 从 SEP 的体外释放（60 分钟内超过 80%）在 0.1N HCl 中显著增强，尽管比液体 SEDDS 慢（5 分钟内超过 80%）。DDB 丸口服后 DDB 的 AUC 在大鼠中表现出比 DDB 丸高 2.36 倍，与液体 SEDDS 相比没有显著差异。总之，我们的研究表明，挤出/球形化技术可以是一种有用的方法来制备这种 SEP，它可能是提高难溶性药物口服生物利用度的一种有前途的方法。
