Chemical and functional analysis of hydroxyurea oral solutions

The primary hypothesis of the upcoming NIH-sponsored phase III infant hydroxyurea (BABY HUG) trial is that hydroxyurea can prevent chronic organ damage in infants with sickle cell anemia. Since hydroxyurea is currently commercially available only in capsules, a liquid formulation of hydroxyurea is needed for young patients. Hydroxyurea oral solutions were prepared by dissolving the contents of the capsules in water (room temperature or mildly heated) with vigorous stirring, filtering excipients, and adding flavored syrup to a final concentration of 100 mg/mL. Chemical stability was determined by measuring the hydroxyurea concentration using a standardized analytical colorimetric analysis, while functional stability was determined by measuring the inhibition of phytohemagglutinin-induced T lymphocyte proliferation. Hydroxyurea oral solutions prepared using room-temperature water had statistically equivalent spectrophotometric concentration and inhibition of T-lymphocyte proliferation for 3 to 6 months. Mild heating of the water to facilitate dissolution of the hydroxyurea capsule contents resulted in a reduced concentration and inhibitory activity of the preparations. Hydroxyurea oral solutions (100 mg/mL) prepared and maintained at room temperature have chemical and functional stability for several months. Hydroxyurea oral solutions prepared and dispensed monthly are suitable for use in the upcoming infant BABY HUG trial.