A Polyvinylpyrrolidone-Based Supersaturable Self-Emulsifying Drug Delivery System for Enhanced Dissolution of Cyclosporine A

Polymers

Young Wook Choi¹  Dae Ro Lee²  Myung Joo Kang²  Myoung Jin Ho² 

[1] College of Pharmacy, Chung-Ang University, 221 Heuksuk-dong, Dongjak-gu, Seoul 156-756, Korea;College of Pharmacy, Dankook University, 119 Dandae-ro, Dongnam-gu, Cheonan, Chungnam 330-714, Korea;

关键词: cyclosporine A;    self-emulsifying drug delivery system (SEDDS);    supersaturation;    apparent concentration;    precipitation inhibitor;    polyvinylpyrrolidone;   

DOI  :  10.3390/polym9040124

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown