Antifungal

Amorphous solid

Engineering

Pharmacokinetics

Materials science

Chromatography

Absorption (acoustics)

Dermatology

Chemical engineering

Bioavailability

Dissolution

Physics

Organic chemistry

Optics

Pharmacology

Composite material

Dispersion (optics)

Medicine

Chemistry

Itraconazole

Crystallinity

European Journal of Pharmaceutical Sciences

The present study was aimed to evaluate the applicability of a self-micellizing solid dispersion (SMSD) system of itraconazole (ITZ) with the use of Soluplus® to achieve improved dissolution and stable oral absorption of ITZ under hypochlorhydric conditions. The SMSD of ITZ (SMSD/ITZ) was prepared by the freeze-drying method. Physicochemical properties of SMSD/ITZ were assessed in terms of morphology, crystallinity, particle size, thermal behavior, dissolution profile, and stability. The pharmacokinetic profile of SMSD/ITZ was evaluated in both normal rats and omeprazole-treated rats as a hypochlorhydric model. From the crystallinity assessment, ITZ in SMSD/ITZ might exist in an amorphous state. The dissolution behavior of SMSD/ITZ was markedly improved under both acidic and neutral conditions through the formation of nano-micelles with a diameter of 127 nm. The degradation of ITZ in SMSD/ITZ was negligible after storage under accelerated conditions at 40 °C or 40 °C/75%RH for 4 weeks. Under light exposure, ca. 33% of ITZ in SMSD/ITZ was degraded, suggesting the need for protection from light. Although the oral absorption of crystalline ITZ was negligible, SMSD/ITZ showed an improved pharmacokinetic profile in normal rats, with an absolute bioavailability (BA) of 2.9%, and even 6.3% in the hypochlorhydric model. From these findings, SMSD technology could be beneficial for improving the absorption profiles of weak basic drugs, even in hypochlorhydric patients.

Improved oral absorption profile of itraconazole in hypochlorhydria by self-micellizing solid dispersion approach