The effect of mucin on supersaturation of poorly water-soluble drugs with different crystallization behavior and in vitro-in vivo correlation

• Published in: Journal of drug delivery science and technology 2022-12, Vol.78, p.103973, Article 103973
• Main Authors: Liu, Weijun, Liu, Jinjin, Wu, Teng, Smyth, Hugh, Cui, Yunfeng
• Format: Article
• Language: English
• Subjects: Crystallization behavior; In vitro-in vivo correlation; Mucin; Poorly water-soluble drug; Supersaturation
• ISSN: 1773-2247
• DOI: 10.1016/j.jddst.2022.103973

Drug delivery systems such as lipids, solid dispersions, or nanocrystals have been proposed to improve the absorption and bioavailability of poorly water-soluble drugs with different crystallization behavior by polymers in a spring-parachute model, which generate and stabilize the drug supersaturation. Mucins, synthesized by specialized epithelial cells, have characteristics of high molecular polymer and electrostatic or hydrophobic interactions with drugs. Our study aims to investigate the effect of mucin on supersaturation of poorly water-soluble drugs with different crystallization behavior in fasted state simulated intestinal fluid (FaSSIF) and in vitro-in vivo correlation (IVIVC). The solubility of poorly water-soluble drugs was tested. The experiment of supersaturation stability was performed by solvent-shift method. The experiment of crystallization was observed by polarized light microscope analysis. The animal pharmacokinetic experiment was conducted, and the IVIVC was analyzed by linear regression. There was no significant difference in solubility between FaSSIF without and with mucin. It showed significant differences in Tss or AUC of naproxen (nifedipine, itraconazole) between FaSSIF without and with mucin (p