Case Study II: High Dose and Solubilization Challenges for an Intravenous Formulation
IriSys was challenged to develop an intravenous formulation of a neutral, poorly water soluble compound at a high dose. IriSys was requested to improve an existing cyclodextrin-drug formulation where a 30% cyclodextrin component provided the high dose concentration requirement. However, there was concern about the toxicity of the high percentage of cyclodextrin increasing potential for a regulatory approval delay. A backup formulation without cyclodextrin and based on surfactants and organic co-solvents was developed. IriSys performed a multivariate solubility and compatibility study in which the variables were co-solvent type, co-solvent concentration, surfactant type, and surfactant concentration. Binary, ternary, and quaternary systems were studied and prototype formulations prepared that were subsequently tested for solubility, pH value, osmolality, and chemical stability. During the study it became apparent that process parameters influenced solubility and stability. These were studied and modified, as appropriate. IriSys successfully eliminated the cyclodextrin from the formulation and was able to increase the drug concentration by 100%.
