Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand.
Eur J Pharm Sci. 2013 Nov 20;50(3-4):459-66. doi: 10.1016/j.ejps.2013.08.006. Epub 2013 Aug 22.
The purpose of this study was to develop self-microemulsifying formulations of an Andrographis paniculata extract in liquid and pellet forms for an improved oral delivery of andrographolide. The optimized liquid self-microemulsifying drug delivery system (SMEDDS) was composed of A. paniculata extract (11.1%), Capryol 90 (40%), Cremophor RH 40 (40%) and Labrasol (8.9%). This liquid SMEDDS was further adsorbed onto colloidal silicon dioxide and microcrystalline cellulose, and converted to SMEDDS pellets by the extrusion/spheronization technique. The microemulsion droplet sizes of the liquid and pellet formulations after dilution with water were in the range of 23.4 and 30.3 nm. The in vitro release of andrographolide from the liquid SMEDDS and SMEDDS pellets was 97.64% (SD 1.97%) and 97.74% (SD 3.36%) within 15 min, respectively while the release from the initial extract was only 10%. The oral absorption of andrographolide was determined in rabbits. The C(max) value of andrographolide from the A. paniculata extract liquid SMEDDS and SMEDDS pellet formulations (equivalent to 17.5mg/kg of andrographolide) was 6-fold and 5-fold greater than the value from the initial extract in aqueous suspension (equivalent to 35 mg/kg of andrographolide), respectively. In addition, the AUC(0-12h) was increased 15-fold by the liquid SMEDDS and 13-fold by the SMEDDS pellets compared to the extract in aqueous suspension, respectively. The results clearly indicated that the liquid and solid SMEDDS could be effectively used to improve the dissolution and oral bioavailability that would also enable a reduction in the dose of the poorly water soluble A. paniculata extract.
本研究旨在开发液体和颗粒形式的穿心莲提取物自微乳制剂,以改善穿心莲内酯的口服递送。优化的液体自微乳药物传递系统(SMEDDS)由穿心莲提取物(11.1%)、Capryol 90(40%)、Cremophor RH 40(40%)和 Labrasol(8.9%)组成。这种液体 SMEDDS 进一步吸附到胶体二氧化硅和微晶纤维素上,并通过挤出/球形化技术转化为 SMEDDS 颗粒。稀释水后,液体和颗粒制剂的微乳液液滴尺寸分别在 23.4nm 和 30.3nm 范围内。液体 SMEDDS 和 SMEDDS 颗粒制剂中穿心莲内酯的体外释放分别在 15 分钟内达到 97.64%(SD 1.97%)和 97.74%(SD 3.36%),而初始提取物的释放仅为 10%。在兔子体内测定了穿心莲内酯的口服吸收。与穿心莲提取物水混悬液(相当于 35mg/kg 的穿心莲内酯)相比,穿心莲提取物液体 SMEDDS 和 SMEDDS 颗粒制剂(相当于 17.5mg/kg 的穿心莲内酯)的 Cmax 值分别增加了 6 倍和 5 倍。此外,与水混悬液相比,液体 SMEDDS 和 SMEDDS 颗粒制剂的 AUC(0-12h)分别增加了 15 倍和 13 倍。结果清楚地表明,液体和固体 SMEDDS 可有效用于提高溶解和口服生物利用度,从而减少水溶性差的穿心莲提取物的剂量。