Patent ID: 8728527

Claim:
An injectable pharmaceutical composition comprising a substantially stable and sterile filterable dispersion of solid nanoparticles in an aqueous medium, wherein the solid nanoparticles comprise a microtubule inhibitor and have a mean particle size of less than 220 nm, wherein the composition is prepared by a process comprising: (a) combining an aqueous phase comprising water and a biocompatible polymer as emulsifier and an organic phase comprising the microtubule inhibitor, a water-immiscible organic solvent, optionally a water-miscible organic solvent as an interfacial lubricant and at least one Ostwald ripening inhibitor; (b) forming an oil-in-water emulsion using a high pressure homogenizer; and (c) removing the water-immiscible organic solvent and the water-miscible organic solvent from the oil-in water emulsion under vacuum; thereby forming a substantially stable dispersion of solid nanoparticles comprising the Ostwald ripening inhibitor, the biocompatible polymeric emulsifier and the microtubule inhibitor in the aqueous medium; wherein (i) the Ostwald ripening inhibitor is a non-polymeric hydrophobic organic compound that is substantially insoluble in water; (ii) the Ostwald ripening inhibitor is less soluble in water than the microtubule inhibitor; (iii) the Ostwald ripening inhibitor is not a phospholipid; and (iv) the Ostwald ripening inhibitor is selected from the group consisting of: (a) a mono-, di- or a tri-glyceride of a fatty acid; (b) a fatty acid mono- or di-ester of a C 2-10 diol; (c) a fatty acid ester of an alkanol or a cycloalkanoyl; (d) a wax; (e) a long chain aliphatic alcohol; (f) a hydrogenated vegetable oil; (g) cholesterol or a fatty acid ester of cholesterol; and (h) combinations thereof.