Novel nano-crystalline solid dispersion of nobiletin with improved dissolution behavior and oral absorption

Abstract

The present study aimed to develop a novel formulation of nobiletin (NOB, a citrus polymethoxylated flavone) by nano-crystalline solid dispersion (nCSD) approach for improving dissolution behavior and oral absorption. NOB-loaded nCSD (nCSD/NOB) was prepared by a wet-milling and freeze-drying systems. Physicochemical properties of nCSD/NOB were characterized in terms of crystallinity, dissolution behavior, particle size distribution, and surface morphology. An analytical method was developed and validated, and a pharmacokinetic study was conducted after oral administration of nCSD/NOB to rats. NOB particles in nCSD/NOB appeared to be crystalline, and the mean diameter was calculated to be ca. 120 nm. In water and acidic condition (pH 1.2), dissolution rates of NOB in nCSD/NOB were ca. 31- and 32-fold higher than those in crystalline NOB, respectively. After oral administration of nCSD/NOB (20 mg-NOB/kg) to rats, nCSD/NOB showed enhanced exposure of NOB compared with crystalline NOB, as evidenced by 12-fold increase of Cmax. The absolute oral bioavailability of NOB in nCSD/NOB was calculated to be ca. 13%, showing 15-fold enhancement compared with that in crystalline NOB. From these findings, the nCSD approach would be efficacious for improving oral absorption of NOB, leading to its enhanced nutraceutical potential.