Lee Dae Ro, Ho Myoung Jin, Choi Young Wook, Kang Myung Joo
College of Pharmacy, Dankook University, 119 Dandae-ro, Dongnam-gu, Cheonan, Chungnam 330-714, Korea.
College of Pharmacy, Chung-Ang University, 221 Heuksuk-dong, Dongjak-gu, Seoul 156-756, Korea.
Polymers (Basel). 2017 Mar 27;9(4):124. doi: 10.3390/polym9040124.
A novel supersaturable self-emulsifying drug delivery system (S-SEDDS) of cyclosporine A (CyA)-a poorly water-soluble immunosuppressant-was constructed in order to attain an apparent concentration⁻time profile comparable to that of conventional SEDDS with reduced use of oil, surfactant, and cosolvent. Several hydrophilic polymers, including polyvinylpyrrolidone (PVP), were employed as precipitation inhibitors in the conventional SEDDS, which consists of corn oil-mono-di-triglycerides, polyoxyl 40 hydrogenated castor oil, ethanol, and propylene glycol. PVP-incorporated pre-concentrate (CyA:vehicle ingredients:PVP = 1:4.5:0.3 w/v/w) spontaneously formed spherical droplets less than 120 nm within 7 min of being diluted with water. In an in vitro dialysis test in a biorelevant medium such as simulated fed and/or fasted state intestinal and/or gastric fluids, PVP-based S-SEDDS exhibited a higher apparent drug concentration profile compared to cellulose derivative-incorporated S-SEDDS, even displaying an equivalent concentration profile with that of conventional SEDDS prepared with two times more vehicle (CyA:vehicle ingredients = 1:9 w/v). The supersaturable formulation was physicochemically stable under an accelerated condition (40 °C/75% RH) over 6 months. Therefore, the novel formulation is expected to be a substitute for conventional SEDDS, offering a supersaturated state of the poorly water-soluble calcinurin inhibitor with a reduced use of vehicle ingredients.
为了在减少油、表面活性剂和助溶剂用量的情况下，获得与传统自乳化药物递送系统（SEDDS）相当的表观浓度-时间曲线，构建了一种新型的环孢素A（CyA，一种难溶性免疫抑制剂）的超饱和自乳化药物递送系统（S-SEDDS）。在由玉米油-甘油一酯-甘油二酯-甘油三酯、聚氧乙烯40氢化蓖麻油、乙醇和丙二醇组成的传统SEDDS中，使用了包括聚乙烯吡咯烷酮（PVP）在内的几种亲水性聚合物作为沉淀抑制剂。含PVP的预浓缩物（CyA:载体成分:PVP = 1:4.5:0.3 w/v/w）在用水稀释后7分钟内自发形成小于120 nm的球形液滴。在生物相关介质（如模拟进食和/或禁食状态的肠液和/或胃液）的体外透析试验中，与含纤维素衍生物的S-SEDDS相比，基于PVP的S-SEDDS表现出更高的表观药物浓度曲线，甚至与用两倍量载体（CyA:载体成分 = 1:9 w/v）制备的传统SEDDS具有相当的浓度曲线。该超饱和制剂在加速条件（40℃/75%相对湿度）下6个月内物理化学性质稳定。因此，这种新型制剂有望替代传统SEDDS，以减少载体成分的用量提供难溶性钙调神经磷酸酶抑制剂的超饱和状态。
