A Four-Component Study for Estimating Solubilities of a Poorly Soluble Compound in Multisolvent Systems Using a Scheffé-Type Model

Abstract

The equilibrium solubility of GF1209184, a poorly soluble compound with potential use as a multidrug resistance (MDR) inhibitor of P-glycoprotein, was studied at 25°C in multisolvent systems containing polyethylene glycol 300, polysorbate 80, ethanol, and water. The objective was to determine the feasibility, with respect to solubility, of formulating a concentrated formulation for product presentation in an ampule or vial. Data were fit to a quadratic Scheffé-type model with excellent correlation between the experimentally determined and fitted equilibrium solubilities (R² = 0.9875, slope = 1.043). Solubilities greater than 4 mg base/mL at 25°C were determined for mixtures in this study, making it feasible, with regard to solubility, to formulate a concentrated vial or ampule formulation. Maximum solubility, however, was dependent on the ability to adjust the apparent pH to ≤3.5 in the cosolvent/surfactant systems studied.