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

Autor: Saori Matsunaga, Yoshiki Seto, Hiroki Suzuki, Hideyuki Sato, Satomi Onoue, Yoshiki Kojo
Rok vydání: 2017
Předmět:
Zdroj: European Journal of Pharmaceutical Sciences. 97:55-61
ISSN: 0928-0987
DOI: 10.1016/j.ejps.2016.10.032
Popis: 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 127nm. The degradation of ITZ in SMSD/ITZ was negligible after storage under accelerated conditions at 40°C or 40°C/75%RH for 4weeks. 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.
Databáze: OpenAIRE
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