RRC ID 51913
Author Kojo Y, Matsunaga S, Suzuki H, Sato H, Seto Y, Onoue S.
Title Improved oral absorption profile of itraconazole in hypochlorhydria by self-micellizing solid dispersion approach.
Journal Eur J Pharm Sci
Abstract 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.
Volume 97
Pages 55-61
Published 2017-1-15
DOI 10.1016/j.ejps.2016.10.032
PII S0928-0987(16)30471-7
PMID 27810562
MeSH Achlorhydria / drug therapy Achlorhydria / metabolism* Administration, Oral Animals Antifungal Agents / administration & dosage Antifungal Agents / chemistry Antifungal Agents / metabolism* Cell Line Drug Liberation / drug effects Drug Liberation / physiology Intestinal Absorption / drug effects Intestinal Absorption / physiology* Intestinal Mucosa / drug effects Intestinal Mucosa / metabolism Itraconazole / administration & dosage Itraconazole / chemistry Itraconazole / metabolism* Male Micelles* Polyethylene Glycols / administration & dosage Polyethylene Glycols / chemistry Polyethylene Glycols / metabolism* Polyvinyls / administration & dosage Polyvinyls / chemistry Polyvinyls / metabolism* Rats Rats, Sprague-Dawley X-Ray Diffraction
IF 3.532
Human and Animal Cells IEC 6(RCB0993)