title: Solubilizing poorly soluble antimycotic agents by emulsification via a solvent-free process.
abstract: The purpose of this study was to formulate itraconazole and ketoconazole as oil/water emulsions for parenteral delivery by using a solvent-free homogenization process, namely SolEmuls (solubilization by emulsification) technology. The drugs were incorporated in the commercial emulsion Lipofundin MCT 20%, composed of a medium-chain triglyceride/long-chain triglyceride (MCT/LCT) oil phase (1:1) and stabilized with 1.2% lecithin. Different parameters such as drug-loading capacity, long-term physical stability, and completeness of drug dissolution were investigated. Up to 10.0 mg/mL complete drug dissolution was achieved with itraconazole; at 20 mg/mL hybrid dispersion was obtained. Itraconazole-loaded emulsions were physically stable for 9 months (data up to now). Ketoconazole showed physical instability in the Lipofundin emulsion, which was stabilized with only 1.2% lecithin. Stabilization of ketoconazole-loaded emulsions was achieved using additionally Tween 80 as steric stabilizer. Higher concentrations of ketoconazole (ie, 10.0 mg/mL concentrated ketoconazole emulsions) were also produced with additional 2.0% Tween 80. Ketoconazole-loaded emulsions, 1 mg/mL, which were stabilized with 2.0% Tween 80, were stable for a period of 6 months. It can be concluded, after formulating amphotericin B and carbamazepine with SolEmuls technology, that SolEmuls was also applicable to the antimycotic agents itraconazole and ketoconazole, yielding IV-applicable emulsions with cost-effective production technologies.
authors.affiliation: Free University of Berlin, Department of Pharmaceutical Technology, Biotechnology and Quality Management, Kelchstrasse 31, 12169 Berlin, Germany.
authors.forename: Aslihan
authors.initials: A
authors.lastname: Akkar
authors.forename: Pawel
authors.initials: P
authors.lastname: Namsolleck
authors.forename: Michael
authors.initials: M
authors.lastname: Blaut
authors.forename: Rainer H
authors.initials: RH
authors.lastname: Müller
mesh_terms: D000935:Antifungal Agents / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D004355:Drug Stability; D004655:Emulsions / Q000737:chemistry*; D017964:Itraconazole / Q000737:chemistry*; D007654:Ketoconazole / Q000737:chemistry*; D009821:Oils / Q000737:chemistry; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D014867:Water / Q000737:chemistry
chemical_list: D000935:Antifungal Agents; D004655:Emulsions; D009821:Oils; D012997:Solvents; D014867:Water; D017964:Itraconazole; D007654:Ketoconazole