Effects of Solvents, Emulsions, Cosolvents, and Complexions on Ex Vivo Mouse Myometrial Contractility

Abstract

A great need exists to develop tocolytic and uterotonic drugs that combat poor, labor-related maternal and fetal outcomes. A widely utilized method to assess novel compounds for their tocolytic and uterotonic efficacy is the isometric organ bath contractility assay. Unfortunately, water-insoluble compounds can be difficult to test using the physiological, buffer-based, organ bath assay. Common methods for overcoming solubility issues include solvent variation, cosolvency, surfactant or complexion use, and emulsification. However, these options for drug delivery or formulation can impact tissue function. Therefore, the goal of this study was to evaluate the ability of common solvents, surfactants, cosolvents, and emulsions to adequately solubilize compounds in the organ bath assay without affecting mouse myometrial contractility. We found that acetone, acetonitrile, and ethanol had the least effect, while dimethylacetamide, ethyl acetate, and isopropanol displayed the greatest inhibition of myometrial contractility based on area under the contractile curve analyses. The minimum concentration of surfactants, cosolvents, and human serum albumin required to solubilize nifedipine, a current tocolytic drug, resulted in extensive bubbling in the organ bath assay, precluding their use. Finally, we report that an oil-in-water base emulsion containing no drug has no statistical effect beyond the control (water), while the drug emulsion yielded the same potency and efficacy as the freely solubilized drug.