Aqueous solvent system for the solubilization of azole compounds

Kristóf Kovács, György Stampf, I. Klebovich, I. Antal, K. Ludányi

Research output: Article

  • 24 Citations

Abstract

Azoles have a wide spectrum antimycotic activity, but due to some derivatives exhibiting poor water solubility their parenteral administration is limited. The influence of solubilizers on the aqueous solubility of the itraconazole, ketoconazole and miconazole was investigated in order to enhance their solubility for a possible parenteral dosage form. The solubilizer effect of acetate, phosphate and gluconate solutions were studied, along with ethanol, glycerol, macrogol 400, propylene glycol and surfactants, such as polysorbate 20, 60, 80 and sodium taurocholeate. The solubilizing effect of these excipients in binary or ternary combinations was also studied. An HPLC method was used for the solubility assay of the azoles. All of the assessed excipients showed considerable solubility enhancement characteristics, moreover the binary and ternary combinations showed synergistic effects solubilizing more miconazole than what they solubilized separately. Ternary combinations were capable of solubilizing more than 30 mg/ml miconazole, and more than 135 mg/ml of ketoconazole, which in both cases is a very substantial increase in solubility compared to their water solubility. The amount of solubilized drugs may well be used therapeutically, and the formulated solvent system can serve as a base for parenteral solutions.

LanguageEnglish
Pages352-358
Number of pages7
JournalEuropean Journal of Pharmaceutical Sciences
Volume36
Issue number2-3
DOIs
Publication statusPublished - febr. 15 2009

Fingerprint

Azoles
Solubility
Miconazole
Ketoconazole
Excipients
Propylene Glycol
Itraconazole
Water
Polysorbates
Dosage Forms
Surface-Active Agents
Glycerol
Acetates
Ethanol
Sodium
Phosphates
High Pressure Liquid Chromatography
Pharmaceutical Preparations

Keywords

    ASJC Scopus subject areas

    • Pharmaceutical Science

    Cite this

    Aqueous solvent system for the solubilization of azole compounds. / Kovács, Kristóf; Stampf, György; Klebovich, I.; Antal, I.; Ludányi, K.

    In: European Journal of Pharmaceutical Sciences, Vol. 36, No. 2-3, 15.02.2009, p. 352-358.

    Research output: Article

    @article{b8be4df03a4745bfbb4d62aefad63eb5,
    title = "Aqueous solvent system for the solubilization of azole compounds",
    abstract = "Azoles have a wide spectrum antimycotic activity, but due to some derivatives exhibiting poor water solubility their parenteral administration is limited. The influence of solubilizers on the aqueous solubility of the itraconazole, ketoconazole and miconazole was investigated in order to enhance their solubility for a possible parenteral dosage form. The solubilizer effect of acetate, phosphate and gluconate solutions were studied, along with ethanol, glycerol, macrogol 400, propylene glycol and surfactants, such as polysorbate 20, 60, 80 and sodium taurocholeate. The solubilizing effect of these excipients in binary or ternary combinations was also studied. An HPLC method was used for the solubility assay of the azoles. All of the assessed excipients showed considerable solubility enhancement characteristics, moreover the binary and ternary combinations showed synergistic effects solubilizing more miconazole than what they solubilized separately. Ternary combinations were capable of solubilizing more than 30 mg/ml miconazole, and more than 135 mg/ml of ketoconazole, which in both cases is a very substantial increase in solubility compared to their water solubility. The amount of solubilized drugs may well be used therapeutically, and the formulated solvent system can serve as a base for parenteral solutions.",
    keywords = "Azole, Co-solvent, Parenteral, pH adjuster, Solubility enhancement, Surfactant",
    author = "Krist{\'o}f Kov{\'a}cs and Gy{\"o}rgy Stampf and I. Klebovich and I. Antal and K. Lud{\'a}nyi",
    year = "2009",
    month = "2",
    day = "15",
    doi = "10.1016/j.ejps.2008.10.007",
    language = "English",
    volume = "36",
    pages = "352--358",
    journal = "European Journal of Pharmaceutical Sciences",
    issn = "0928-0987",
    publisher = "Elsevier",
    number = "2-3",

    }

    TY - JOUR

    T1 - Aqueous solvent system for the solubilization of azole compounds

    AU - Kovács, Kristóf

    AU - Stampf, György

    AU - Klebovich, I.

    AU - Antal, I.

    AU - Ludányi, K.

    PY - 2009/2/15

    Y1 - 2009/2/15

    N2 - Azoles have a wide spectrum antimycotic activity, but due to some derivatives exhibiting poor water solubility their parenteral administration is limited. The influence of solubilizers on the aqueous solubility of the itraconazole, ketoconazole and miconazole was investigated in order to enhance their solubility for a possible parenteral dosage form. The solubilizer effect of acetate, phosphate and gluconate solutions were studied, along with ethanol, glycerol, macrogol 400, propylene glycol and surfactants, such as polysorbate 20, 60, 80 and sodium taurocholeate. The solubilizing effect of these excipients in binary or ternary combinations was also studied. An HPLC method was used for the solubility assay of the azoles. All of the assessed excipients showed considerable solubility enhancement characteristics, moreover the binary and ternary combinations showed synergistic effects solubilizing more miconazole than what they solubilized separately. Ternary combinations were capable of solubilizing more than 30 mg/ml miconazole, and more than 135 mg/ml of ketoconazole, which in both cases is a very substantial increase in solubility compared to their water solubility. The amount of solubilized drugs may well be used therapeutically, and the formulated solvent system can serve as a base for parenteral solutions.

    AB - Azoles have a wide spectrum antimycotic activity, but due to some derivatives exhibiting poor water solubility their parenteral administration is limited. The influence of solubilizers on the aqueous solubility of the itraconazole, ketoconazole and miconazole was investigated in order to enhance their solubility for a possible parenteral dosage form. The solubilizer effect of acetate, phosphate and gluconate solutions were studied, along with ethanol, glycerol, macrogol 400, propylene glycol and surfactants, such as polysorbate 20, 60, 80 and sodium taurocholeate. The solubilizing effect of these excipients in binary or ternary combinations was also studied. An HPLC method was used for the solubility assay of the azoles. All of the assessed excipients showed considerable solubility enhancement characteristics, moreover the binary and ternary combinations showed synergistic effects solubilizing more miconazole than what they solubilized separately. Ternary combinations were capable of solubilizing more than 30 mg/ml miconazole, and more than 135 mg/ml of ketoconazole, which in both cases is a very substantial increase in solubility compared to their water solubility. The amount of solubilized drugs may well be used therapeutically, and the formulated solvent system can serve as a base for parenteral solutions.

    KW - Azole

    KW - Co-solvent

    KW - Parenteral

    KW - pH adjuster

    KW - Solubility enhancement

    KW - Surfactant

    UR - http://www.scopus.com/inward/record.url?scp=58149164902&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=58149164902&partnerID=8YFLogxK

    U2 - 10.1016/j.ejps.2008.10.007

    DO - 10.1016/j.ejps.2008.10.007

    M3 - Article

    VL - 36

    SP - 352

    EP - 358

    JO - European Journal of Pharmaceutical Sciences

    T2 - European Journal of Pharmaceutical Sciences

    JF - European Journal of Pharmaceutical Sciences

    SN - 0928-0987

    IS - 2-3

    ER -