Carboxymethyl Ethylcellulose Acts as a Solid Dispersion Carrier with a Remarkably Higher Improvement Effect on Dissolution-Permeation of Itraconazole

Abstract

This study aimed to investigate solid dispersion formulations of itraconazole (ITZ) by using carboxymethyl ethylcellulose (CMEC) as an enteric cellulose derivative to improve stability, dissolution, and permeation profiles. Polyvinylpyrrolidone covinyl acetate (PVPVA) and hydroxypropyl methylcellulose acetate succinate (HPMCAS) were used as traditional carriers. Ball-milling successfully induced the formation of solid dispersions of ITZ with the used polymers, resulting in single-glass transition temperatures. The infrared spectra suggested the formation of hydrogen bonding between ITZ and each polymer. Water sorption of CMEC was comparable to that of HPMCAS, which was significantly lower than that of PVPVA, enabling the maintenance of the amorphous state of the solid dispersion under 40 °C/75% relative humidity. The dissolution-permeation profiles of amorphous ITZ were improved in the solid dispersions with PVPVA or HPMCAS, and further enhancement was obtained through combination with CMEC. The antiprecipitation effect of the polymers on the supersaturated ITZ was in the same order as the dissolution-permeation test. The improvement mechanisms of the dissolution-permeation and antiprecipitation effect of CMEC could be explained by the prevention effect on the growth of the size of the drug-rich colloids of ITZ via the supersaturated condition. We conclude that CMEC has big potential as a solid dispersion carrier.