Abstract: Improved cleanability and contamination prevention are provided in a wet milling apparatus for the production of pharmaceutical grade milled products. The advantages are provided by a milling agitator that is characterized by a smooth, seamless agitating surface, without crevices or seams which might accumulate contamination and which might prevent removal of contamination during cleaning. The use of polymeric milling media reduces wear on the agitator and permits the agitator to be constructed with permanent, smooth welded joints. Seamless joints are also provided on the interior of the milling chamber and sanitary, threadless fasteners are provided for the media separation screen and other milling chamber fittings.

Abstract: A method of preparing submicron particles of a therapeutic or diagnostic agent which comprises grinding the agent in the presence of grinding media having a mean particle size of less than about 75 microns. In a preferred embodiment, the grinding media is a polymeric resin. The method provides extremely fine particles, e.g., less than 100 nanometers in size, free of unacceptable contamination.

Abstract: A continuous method of preparing submicron particles of a therapeutic or diagnostic agent comprises the steps of continuously introducing the agent and rigid grinding media into a milling chamber, contacting the agent with the grinding media while in the chamber to reduce the particle size of the agent, continuously removing the agent and the grinding media from the milling chamber, and thereafter separating the agent from the grinding media. In a preferred embodiment, the grinding media is a polymeric resin having a mean particle size of less than 300 .mu.m. In another preferred embodiment, the agent, grinding media and a liquid dispersion medium are continuously introduced into the milling chamber. In a further embodiment, the agent and grinding media are recirculated through the milling chamber. The method enables the use of fine grinding media, e.g., of a particle size of less than about 300 .mu.m, in a continuous grinding process which provides extremely fine particles of the agent, e.g.

Abstract: A process for dispersing a particulate solid substance in a continuos aqueous phase comprising the steps of:providing a comminution reactor;providing a particulate solid substance comprising a weak acid functional group, having effective pK.sub.a1 >1 and less than 1% by weight aqueous solubility at pH=pK.sub.a1 ;providing an aqueous solution consisting essentially of water or a mixture of water with water-miscible solvent, at pH less than the greater of 7 and pK.sub.a1 +2;providing a buffering salt of a weak acid, where the weak acid associated with this buffering salt has pK.sub.a2 and wherepK.sub.a1 -2.ltoreq.pK.sub.a2 ;providing milling media;combining said particulate solid substance, said aqueous solution, said buffering salt, and said milling media in said comminution reactor to produce a multiphase mixture; andmilling said mixture to produce a reduced particle size slurry of said particulate solid substance is disclosed.

Abstract: A process for forming a nanocrystalline dispersion of a photographically useful compound in a continuous phase comprising the steps of:providing a nanoamorphous dispersion of said photographically useful compound in said continuous phase, andannealing said nanoamorphous dispersion to transform the physical state of said chemical compound therein to a crystalline physical state and to thereby obtain a nanocrystalline dispersion is disclosed.

Abstract: A continuous method of preparing submicron particles of a compound useful in imaging elements (or other materials, such as pigments, etc.) comprises the steps of continuously introducing the compound and rigid milling media into a milling chamber, contacting the compound with the milling media while in the chamber to reduce the particle size of the compound, continuously removing the compound and the milling media from the milling chamber, and thereafter separating the compound from the milling media. In a preferred embodiment, the milling media is a polymeric resin having a mean particles size of less than 300 .mu.m. The method enables the use of fine milling media in a continuous milling process which provides extremely fine particles of the compound useful in imaging elements while avoiding problems, e.g., separator screen plugging associated with prior art processes requiring the separation of compound from the milling media in the milling chamber.

Abstract: A method of preparing submicron particles of a material, such as a pigment useful in paints or a compound useful in imaging elements, which comprises milling the agent in the presence of milling media having a mean particle size of less than about 100 microns. In a preferred embodiment, the milling media is a polymeric resin. The method provides extremely fine particles, e.g., less than 100 nm in size, free of unacceptable contamination.

Abstract: Particles of compound useful in imaging elements are milled using a milling media comprising a polymeric resin. The use of polymeric milling media permits the production of particles having an average particle size less than 1 micron. Further, the resulting particles are free from the contamination resulting from conventional milling media of, for example, glass, ceramic or steel.

Abstract: An apparatus for producing amorphous particle dispersions of high-melting microcrystalline solids in a continuous process. The apparatus comprises a pump, two heat exchangers, a back-pressure valve and conduits connecting them, whereby it is possible to make aqueous dispersions of particles whose melting points are above 100.degree. C.

Abstract: There is provided a water based water repellent coating composition, method of making and method of use. The coating composition comprises an emulsion having water as the continuous phase and, as the discontinuous phase, droplets of a nonvolatile organic water repellent composition, the emulsion containg an emulsion stabilizing amount of a hydrophobically modified polyacrylic acid polymer wherein the viscosity of the emulsion is less than about 100 Cps and the particle size of the droplets is less than about 50 microns. The relatively low viscosity and small particle size provides for easy application and excellent penetration into porous substrates. The process of making the compositions involves the making of a conventional emulsion of this type and then high kinetic energy processing so as to produce the desired viscosity and particle size. The method of use involves the application of the composition to a substrate followed by evaporation of the water and any volatile components from the composition.

Abstract: An in-line process for mixing solvents with amorphous particle dispersions is disclosed. Continuous emulsification of the solvent is achieved by an in-line high-shear mixer, and diffusion of solvent to the amorphous particles is controlled in a plug flow reactor. Both processes are conducted in-line during dispersion delivery to coating processes. An apparatus for carrying out the process is also disclosed.

Abstract: Dispersible particles consisting essentially of a crystalline drug substance having a surface modifier adsorbed on the surface thereof in an amount sufficient to maintain an effective average particle size of less than about 400 nm, methods for the preparation of such particles and dispersions containing the particles. Pharmaceutical compositions containing the particles exhibit unexpected bioavailability and are useful in methods of treating mammals.

Abstract: An object of the invention is to overcome disadvantages of prior practices. A further object of the invention is to provide a process for providing particles that result in improved UV absorption in photographic products.An additional object is to provide lower cost polymer particle dispersions.The invention is generally accomplished by mechanically grinding a crystalline material to a desired particle size in a liquid that is not a solvent for the material, heating said crystalline particles dispersed in said liquid to above their melting temperature, and cooling the melted particles in said liquid to form amorphous particles. In preferred forms of the invention, the material is a photographically useful material, such as ultraviolet light absorber or coupler.