Abstract: This invention describes the preparation of nanoparticulate pharmaceutical agent dispersion via a process that comprises the dissolution of the said pharmaceutical agent in an alkaline solution and then neutralizing the said solution with an acid in the presence of suitable surface-modifying, surface-active agents to form a fine particle dispersion of the said pharmaceutical agent. A combination of surface active surface modifying agents comprising a nonionic surface active substance and an anionic surface active material having a chemical structure which is at least on a molecular basis 75% similar to the pharmaceutical agent is used. This process is preferably followed by steps of diafiltration clean-up of the dispersion and then concentration of it to a desired level. This process of dispersion preparation leads to microcrystalline particles of Z-average diameters smaller than 400 nm as measured by photon correlation spectroscopy.

Abstract: It has been known that administration of pharmaceutical agents (both diagnostic and therapeutic) with poor water solubility in the form of particles less than 400 nm in diameter produces agent formulation with increased bioavailibility. Bioavailability being proportional to the surface area, increases with reduction of particle size of the dispersed agent. We have discovered that chemical derivatization of certain photographic coupler molecules with chemical moiety that are capable of functioning as pharmaceutical agents (both diagnostic and therapeutic) is amenable to the preparation of nanoparticulate pharmaceutical agent dispersions via a process that comprises the dissolution of the said pharmaceutical agent in an alkaline solution and then neutralizing the said solution with an acid in the presence of a suitable surface-modifying, surface-active agent to form an ultra fine particle dispersion of the said pharmaceutical agent.