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Solubilizing poorly soluble antimy cotic agents by emulsification via a solvenent-free process

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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.

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Authors and Affiliations

  1. Department of Pharmaceutical Technology, Biotechnology and Quality Management, Free University of Berlin, Kelchstrasse 31, 12161, Berlin, Germany

    Aslihan Akkar

  2. Department of Gastrointestinal Microbiology, German Institute of Human Nutrition, Arthur-Scheunert-Allee, 114-116, 14558, Bergholz-Rehbrücke, Germany

    Pawel Namsolleck & Michael Blaut

  3. Pharmasol GmbH, Blohmstrasse 66a, 12307, Berlin, Germany

    Rainer H. Müller

Authors
  1. Aslihan Akkar
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  2. Pawel Namsolleck
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  3. Michael Blaut
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  4. Rainer H. Müller
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Correspondence to Rainer H. Müller.

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Akkar, A., Namsolleck, P., Blaut, M. et al. Solubilizing poorly soluble antimy cotic agents by emulsification via a solvenent-free process. AAPS PharmSciTech 5, 24 (2004). https://doi.org/10.1208/pt050124

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