Avoidance of food effect on oral absorption profile of itraconazole by self-micellizing solid dispersion approach. Issue 5 (October 2017)

• Record Type: Journal Article
• Authors: Kojo, Yoshiki; Kobayashi, Kanako; Matsunaga, Saori; Suzuki, Hiroki; Seto, Yoshiki; Sato, Hideyuki; Onoue, Satomi
• Is Part Of: Drug metabolism and pharmacokinetics. Volume 32:Issue 5(2017)
• Page Start: 273
• Page End: 276
• Publication Date: 2017-10
• Subjects: Biorelevant media -- Dissolution -- Food effect -- Itraconazole -- Oral bioavailability -- Self-micellizing solid dispersion; AUC0–2 area under the curve of dissolved itraconazole vs. time from 0 to 2 h -- AUC0–∞ area under the curve of blood concentration vs. time from 0 h to infinity -- BA bioavailability -- BCS biopharmaceutical classification system -- DMSO dimethyl sulfoxide -- FaSSGF fasted-state simulated gastric fluid -- FaSSIF fasted-state simulated intestinal fluid -- FeSSGF fed-state simulated gastric fluid -- FeSSIF fed-state simulated intestinal fluid -- GI gastrointestinal -- IS internal standard -- ITZ itraconazole -- PK pharmacokinetic -- SD solid dispersion -- SGF simulated gastric fluid -- SIF simulated intestinal fluid -- SMSD self-micellizing solid dispersion -- SMSD/ITZ self-micellizing solid dispersion of itraconazole -- TEM transmission electron microscopy -- Tmax time to maximum concentration -- UPLC/ESI-MS ultra-performance liquid chromatography equipped with electrospray ionization mass spectrometry; Drugs -- Metabolism -- Periodicals; Pharmacokinetics -- Periodicals; 615.7
• DOI: 10.1016/j.dmpk.2017.06.001
• Languages: English
• ISSNs: 1347-4367

Abstract

Abstract: The present study was aimed to avoid pharmacokinetic transitions of itraconazole (ITZ) evoked by high-fat meal intake by employing a self-micellizing solid dispersion (SMSD) approach. The dissolution behavior of SMSD/ITZ was assessed in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). To evaluate the food effect on the oral absorption profile of ITZ, a pharmacokinetic study was conducted on orally-dosed ITZ samples in fasted and high-fat meal-fed rats. Crystalline ITZ showed a 9.0-fold higher dissolution amount of ITZ in fed-state SGF (FeSSGF) than in fasted-state SGF (FaSSGF), whereas there was no significant difference in the dissolution amount of ITZ in SMSD/ITZ between FeSSGF and FaSSGF. In fed- and fasted-state SIF, SMSD/ITZ exhibited reduced variation of ITZ dissolution, possibly leading to suppression of the food effect on the dissolution behavior of ITZ. After the oral administration of crystalline ITZ to high-fat meal-fed rats, the oral bioavailability of ITZ was 14-fold higher than that in fasted rats. In contrast, orally-dosed SMSD/ITZ in fed rats exhibited limited transition of pharmacokinetic behavior regardless of food intake due to the improvement in the dissolution behavior of ITZ even under fasted conditions. SMSD technology could be an efficacious dosage option for the consistent oral absorption and clinical outcomes of ITZ. Graphical abstract: