Floating drug delivery system of itraconazole: Formulation, in vitro and in vivo studies

• Published in: Journal of drug delivery science and technology 2019-02, Vol.49, p.491-501
• Main Authors: Gökbulut, Eda, Vural, İmran, Aşıkoğlu, Makbule, Özdemir, Nurten
• Format: Article
• Language: English
• Subjects: Caco-2 permeability; Cyclodextrin complex; Floating microspheres/beads; Gamma scintigraphy; Ionotropic gelation; Itraconazole
• ISSN: 1773-2247
• DOI: 10.1016/j.jddst.2018.12.019

A multiple unit oral floating drug delivery system of itraconazole was developed to prolong gastric residence time, target stomach mucosa and increase drug bioavailability. To prepare non-effervescent floating microspheres/beads, ionotropic gelation method was used. Since the solubility of itraconazole is low at pH 1.2, it was attempted to increase the solubility by preparing inclusion complexes using randomly methylated beta-cyclodextrin and with polyvinylpyrrolidone cross linked and starch. In this study, the effects of formulation parameters like, concentration and types of polymer, crosslinking agent and the excipients, the floating ability, surface characteristics and drug release profiles were investigated. Optimum formulation (NG17) was used for Caco-2 cell culture studies. In permeability studies, at pH 5, 6 and 7.4, the formulation NG17 at pH 5, which is the pH of the proximal region of small intestine (absorption window of itraconazole), showed the highest permeability value which is 5.88 × 10−6 cm/s. NG17 was also used for in vivo imaging studies. It was conducted in rabbits by using gamma scintigraphy and obtained that NG17 floated for 6.5 h in the stomach. As a result, it was found that, with non-effervescent floating bead formulations, the bioavailability of itraconazole can be improved. [Display omitted]