title: Development of novel itraconazole-loaded solid dispersion without crystalline change with improved bioavailability.
abstract: To develop a novel itraconazole-loaded solid dispersion without crystalline change with improved bioavailability, various itraconazole-loaded solid dispersions were prepared with water, polyvinylpyrroline, poloxamer and citric acid. The effect of carriers on aqueous solubility of itraconazole was investigated. Their physicochemical properties were investigated using SEM, DSC, and powder X-ray diffraction. The dissolution, bioavailability in rats and stability of solid dispersions were evaluated. Unlike conventional solid dispersion system, the itraconazole-loaded solid dispersion with relatively rough surface did not change crystalline form of drug. Our DSC and powder X-ray diffraction results suggested that this solid dispersion was formed by attaching hydrophilic carriers to the surface of drug without crystal change, resulting in conversion of the hydrophobic drug to hydrophilic form. The itraconazole-loaded solid dispersion at the weight ratio of itraconazole/polyvinylpyrroline/poloxamer of 10/2/0.5 gave maximum drug solubility of about 20 microg/mL. It did not change the crystalline form of drug for at least 6 months, indicating that it was physically stable. It gave higher AUC, C(max) and T(max) compared to itraconazole powder and similar values to the commercial product, suggesting that it was bioequivalent to commercial product in rats. Thus, it would be useful to deliver a poorly water-soluble itraconazole without crystalline change with improved bioavailability.
authors.affiliation: Research Center, Samil Pharmaceutical Co. Ltd., Anyang, 431-060, Korea.
authors.forename: Young-Joon
authors.initials: YJ
authors.lastname: Park
authors.forename: Jing Ji
authors.initials: JJ
authors.lastname: Xuan
authors.forename: Dong Hoon
authors.initials: DH
authors.lastname: Oh
authors.forename: Prabagar
authors.initials: P
authors.lastname: Balakrishnan
authors.forename: Ho-Joon
authors.initials: HJ
authors.lastname: Yang
authors.forename: Woo Hyun
authors.initials: WH
authors.lastname: Yeo
authors.forename: Mi-Kyung
authors.initials: MK
authors.lastname: Lee
authors.forename: Han-Gon
authors.initials: HG
authors.lastname: Choi
authors.forename: Chul Soon
authors.initials: CS
authors.lastname: Yong
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D019343:Citric Acid / Q000737:chemistry; D003460:Crystallization; D004337:Drug Carriers / Q000737:chemistry*; D004355:Drug Stability; D004356:Drug Storage; D057927:Hydrophobic and Hydrophilic Interactions; D017964:Itraconazole / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D008855:Microscopy, Electron, Scanning; D020442:Poloxamer / Q000737:chemistry; D011205:Povidone / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D014961:X-Ray Diffraction
chemical_list: D000935:Antifungal Agents; D004337:Drug Carriers; D020442:Poloxamer; D019343:Citric Acid; D017964:Itraconazole; D011205:Povidone