| Abstract: | A novel technique was developed to quantify the solubility of pharmaceutical actives in semisolid formulations. Ointments and emulsions of increasing potencies were sheared to disrupt their internal microcrystalline networks. These sheared materials were held in taut cheesecloth pouches, and the bleed that percolated out was collected and assayed for active potency. The solute concentration in the bleed was proportional to the concentration of the solute in solution in the formulation. Plots of bleed active potency against total formulation potency rose linearly to the point of formulation saturation. Above saturation, bleed potencies remained constant, producing plateaus on the solubility plots. The formulation potency at the onset of plateau quantified the saturation solubility of the active in each formulation. This technique was demonstrated with butylparaben in three ointment bases, and with hydrocortisone in an emulsion formulation. The solubility estimates thus obtained were confirmed experimentally by optical microscopy. This novel technique permits saturation solubilities to be determined for a range of semisolid formulations, with much greater accuracy than was previously possible. |
