Development and evaluation of self-microemulsifying liquid and pellet formulations of curcumin, and absorption studies in rats.
This study describes the development and characterization of self-microemulsifying drug delivery systems (SMEDDS) in liquid and pellet forms that result in improved solubility, dissolution, and in vivo oral absorption of the poorly water-soluble compound curcumin. Solubility of curcumin was determined in various vehicles, including oils, surfactants and co-surfactants. Pseudo-ternary phase diagrams were constructed to identify the most efficient self-emulsification region. The optimized SMEDDS used for curcumin formulations in liquid and pellet forms contained 70% mixtures of two surfactants: Cremophor EL and Labrasol (1:1), and 30% mixtures of oil: Labrafac PG and Capryol 90 (1:1). The curcumin-SMEDDS in liquid and pellet formulations rapidly formed fine oil-in-water microemulsions, with particle size ranges of 25.8-28.8 nm and 29.6-32.8 nm, respectively. The in vitro rate and extent of release of curcumin from liquid SMEDDS and SMEDDS pellets was about 16-fold higher than that of unformulated curcumin. Plasma concentration-time profiles from pharmacokinetic studies in rats dosed with liquid and pelleted SMEDDS showed 14- and 10-fold increased absorption of curcumin, respectively, compared to the aqueous suspensions of curcumin. Curcumin-SMEDDS liquid and curcumin-SMEDDS pellets were found to be stable up to 6 months under intermediate and accelerated conditions. These studies demonstrate that the new self-microemulsifying systems in liquid and pellet forms are promising strategies for the formulation of poorly soluble lipophilic compounds with low oral bioavailability.
Setthacheewakul
Saipin
S
Department of Pharmaceutical Technology, Prince of Songkla University, Songkhla, Thailand.
Mahattanadul
Sirima
S
Phadoongsombut
Narubodee
N
Pichayakorn
Wiwat
W
Wiwattanapatapee
Ruedeekorn
R
D000042:Absorption; D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D001682:Biological Availability; D003474:Curcumin / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems; D004343:Drug Implants; D004355:Drug Stability; D045703:Emulsifying Agents; D004655:Emulsions; D008297:Male; D009821:Oils; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013501:Surface-Active Agents
D000970:Antineoplastic Agents; D004343:Drug Implants; D045703:Emulsifying Agents; D004655:Emulsions; D009821:Oils; D013501:Surface-Active Agents; D003474:Curcumin