title: Composition optimization and stability testing of a parenteral antifungal solution based on a ternary solvent system.
abstract: An intravenous solution is a dosage forms intended for administration into the bloodstream. This route is the most rapid and the most bioavailable method of getting drugs into systemic circulation, and therefore it is also the most liable to cause adverse effects. In order to reduce the possibility of side effects and to ensure adequate clinical dosage of the formulation, the primarily formulated composition should be optimized. It is also important that the composition should retain its therapeutic effectiveness and safety throughout the shelf-life of the product. This paper focuses on the optimization and stability testing of a parenteral solution containing miconazole and ketoconazole solubilized with a ternary solvent system as model drugs. Optimization of the solvent system was performed based on assessing the risk/benefit ratio of the composition and its properties upon dilution. Stability tests were conducted based on the EMEA (European Medicines Agency) "guideline on stability testing: stability testing of existing active substances and related finished products". Experiments show that both the amount of co-solvent and surface active agent of the solvent system could substantially be reduced, while still maintaining adequate solubilizing power. It is also shown that the choice of various containers affects the stability of the compositions. It was concluded that by assessing the risk/benefit ratio of solubilizing power versus toxicity, the concentration of excipients could be considerably decreased while still showing a powerful solubilizing effect. It was also shown that a pharmaceutically acceptable shelf-life could be assigned to the composition, indicating good long-term stability.
authors.affiliation: Department of Pharmaceutics, Semmelweis University, 7-9 Hogyes E. Street, H-1092, Budapest, Hungary. kovkrist@gytk.sote.hu
authors.forename: Kristóf
authors.initials: K
authors.lastname: Kovács
authors.forename: István
authors.initials: I
authors.lastname: Antal
authors.forename: György
authors.initials: G
authors.lastname: Stampf
authors.forename: Imre
authors.initials: I
authors.lastname: Klebovich
authors.forename: Krisztina
authors.initials: K
authors.lastname: Ludányi
mesh_terms: D004304:Dosage Forms; D004333:Drug Administration Routes; D005079:Excipients / Q000737:chemistry; D007263:Infusions, Parenteral; D007654:Ketoconazole / Q000737:chemistry; D008825:Miconazole / Q000737:chemistry; D004364:Pharmaceutical Preparations / Q000032:analysis; D019999:Pharmaceutical Solutions; D012996:Solutions / Q000737:chemistry; D012997:Solvents / Q000737:chemistry*; D013501:Surface-Active Agents / Q000737:chemistry
chemical_list: D004304:Dosage Forms; D005079:Excipients; D004364:Pharmaceutical Preparations; D019999:Pharmaceutical Solutions; D012996:Solutions; D012997:Solvents; D013501:Surface-Active Agents; D008825:Miconazole; D007654:Ketoconazole