Hydroxyurea, a chemically hydroxylated derivative of the symmetrical urea is currently under investigation for administration to pediatric patients suffering from sickle cell anemia. The PIB clinical formulation contains sodium benzoate as a preservative and needed to be changed because the commercial syrup diluent has replaced sodium benzoate with methylparaben. A 23 screening factorial design matrix with nine different combinations was used to study the compatibility of methylparaben with hydroxyurea and excipients in open cap storage condition (40°C/75%RH) for 4 weeks. The compatibility of hydroxyurea with excipients in closed cap conditions at 30°C/65%RH and 40°C/75%RH storage for up to 6 weeks was also studied. The nine different hydroxyurea blend combinations were tested for physical appearance, thermal properties (differential scanning calorimetry), pH (blend reconstituted in Humco® simple syrup), moisture content, microbial limit testing (MLT), and antimicrobial effectiveness testing (AET). An HPLC method was developed for assaying hydroxyurea.
Director, Formulations R&D, Pharmaceutical Sciences