Aqueous solvent system for the solubilization of azole compounds.
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.
Kovács
Kristóf
K
Department of Pharmaceutics, Semmelweis University, 7-9 Hogyes E. street, H-1092 Budapest, Hungary. kovkrist@gytk.sote.hu
Stampf
György
G
Klebovich
Imre
I
Antal
István
I
Ludányi
Krisztina
K
D000085:Acetates / Q000737:chemistry; D001393:Azoles / Q000737:chemistry*; D002125:Calcium Gluconate / Q000737:chemistry; D000431:Ethanol / Q000737:chemistry; D005990:Glycerol / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D017964:Itraconazole / Q000737:chemistry; D007654:Ketoconazole / Q000737:chemistry; D008825:Miconazole / Q000737:chemistry; D010756:Phosphoric Acids / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011136:Polysorbates / Q000737:chemistry; D019946:Propylene Glycol / Q000737:chemistry; D012995:Solubility; D012997:Solvents / Q000737:chemistry*; D013501:Surface-Active Agents / Q000737:chemistry; D014867:Water / Q000737:chemistry*
D000085:Acetates; D001393:Azoles; D010756:Phosphoric Acids; D011136:Polysorbates; D012997:Solvents; D013501:Surface-Active Agents; D014867:Water; D017964:Itraconazole; D000431:Ethanol; D011092:Polyethylene Glycols; D019946:Propylene Glycol; D008825:Miconazole; C030242:phosphoric acid; D005990:Glycerol; D007654:Ketoconazole; C018824:ammonium acetate; D002125:Calcium Gluconate