Reduced food-effect and enhanced bioavailability of a self-microemulsifying formulation of itraconazole in healthy volunteers

• Published in: European journal of pharmaceutical sciences Vol. 33; no. 2; pp. 159 - 165
• Main Authors: Woo, Jong Soo, Song, Yun-Kyoung, Hong, Ji-Yeon, Lim, Soo-Jeong, Kim, Chong-Kook
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier B.V 05.02.2008; Elsevier
• Subjects: Administration, Oral; Adult; Area Under Curve; Bioavailability; Biological and medical sciences; Biological Availability; Drug Delivery Systems - methods; Emulsions; Fasting - metabolism; Food-Drug Interactions; Food-effect; General pharmacology; Humans; Itraconazole; Itraconazole - administration & dosage; Itraconazole - blood; Itraconazole - pharmacokinetics; Male; Medical sciences; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Self-microemulsifying drug delivery systems; Food-effect; Bioavailability; Self-microemulsifying drug delivery systems; Itraconazole; Human; Pharmaceutical technology; Healthy subject; Drug carrier; Antifungal agent; Formulation; Triazole derivatives; Pharmacokinetics; Food
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2007.11.001

Self-microemulsifying drug delivery systems (SMEDDS) represent a possible alternative to traditional oral formulations of lipophilic compounds. This study was designed to compare the oral bioavailability and food-effect of SMEDDS of itraconazole (ITRA-GSMP capsule containing 50 mg itraconazole) to that of the currently marketed formulation (Sporanox capsule containing 100 mg itraconazole). Eight healthy volunteers received Sporanox or ITRA-GSMP capsule in the fasted state or after a high-fat diet on four separate dosing occasions with a 2-week washout period. Blood samples were collected and analyzed. After administration of the ITRA-GSMP capsule, AUC 0–24 and C max were 1.9- and 2.5-fold higher in the fasted state and 1.5- and 1.3-fold higher in the fed state, respectively, than those of the Sporanox capsule. Moreover, ITRA-GSMP capsules yielded more reproducible blood-time profiles than Sporanox capsules. Food had a marked effect on itraconazole absorption from the Sporanox capsule, whereas the influence was less pronounced for the ITRA-GSMP capsule. Collectively, our data suggest that a new self-microemulsifying formulation may provide an alternative oral formulation for itraconazole with improved oral bioavailability and reduced food-effect.