Abstract: Drug substances, which comprise a solid amorphous forms of a compound of structural formula I and have a BET specific surface area of up to about 94 m2/g, pharmaceutical compositions comprising such drug substances, processes for preparing such drug substances and uses of such drug substances and pharmaceutical compositions are disclosed.

Abstract: The present invention provides a method of continuous precipitation and isolation of an amorphous solid particulate form of 3-[2-(3-tert-Butyl-ureido)-3,3-dimethyl-butyryl]-6,6-dimethyl-3-aza-bicyclo[3.1.0]hexane-2-carboxylic acid (2-carbamoyl-1-cyclobutylmethyl-2-oxo-ethyl)-amide having controlled physical properties. The present invention provides also pharmaceutical formulations comprising the precipitated compound.

Abstract: The present invention provides a method of continuous precipitation and isolation of an amorphous solid particulate form of 3-[2-(3-tert-Butyl-ureido)-3,3-dimethyl-butyryl]-6,6-dimethyl-3-aza-bicyclo[3.1.0]hexane-2-carboxylic acid (2-carbamoyl-1-cyclobutylmethyl-2-oxo-ethyl)-amide having controlled physical properties. The present invention provides also pharmaceutical formulations comprising the precipitated compound.

Abstract: A solid hollow fiber cooling crystallizer and method for crystallizing aqueous and organic solutions are provided. The solid hollow fiber crystallizer (SHFC) for carrying out cooling crystallization of inorganic/organic microsolutes/macrosolutes from solution generally includes a bundle of non-porous hollow fibers mounted within a shell where a feed solution for crystallization flows through the lumen side of the hollow fibers and a cooling solution flows through the shell side to form nuclei and subsequently crystals in the feed solution at a temperature below its saturation temperature. The solid hollow fiber crystallizer may be combined with a mixing device, such as a completely stirred tank or static mixer, to further effectuate crystallization. The solid hollow fiber crystallizer may be operated in a number of modes including feed recycle mode, once through mode, SHFC-in-line static mixer in series mode, and SHFC-CST in series mode.

Abstract: Antisolvent crystallization systems and methods are provided that employ porous hollow fiber membranes. The porous hollow fiber membrane includes a plurality of porous hollow fibers positioned within a shell, each porous hollow fiber defining a lumen side and shell side. A crystallizing solution is introduced to one side of the hollow fibers and an antisolvent is introduced to the other side of the fibers, in either cocurrent or countercurrent flow. One of the antisolvent and the crystallizing solution permeates in part through the porous hollow fiber membrane to the other side and crystals are formed thereby. Permeation of the antisolvent or the crystallizing solution establishes advantageous radial mixing that facilitates crystal formation of a desired size distribution. Downstream mixing, e.g., a completely stirred tank or a static mixer, may be employed to further improve crystallization operations.

Abstract: A solid hollow fiber cooling crystallizer and method for crystallizing aqueous and organic solutions are provided. The solid hollow fiber crystallizer (SHFC) for carrying out cooling crystallization of inorganic/organic microsolutes/macrosolutes from solution generally includes a bundle of non-porous hollow fibers mounted within a shell where a feed solution for crystallization flows through the lumen side of the hollow fibers and a cooling solution flows through the shell side to form nuclei and subsequently crystals in the feed solution at a temperature below its saturation temperature. The solid hollow fiber crystallizer may be combined with a mixing device, such as a completely stirred tank or static mixer, to further effectuate crystallization. The solid hollow fiber crystallizer may be operated in a number of modes including feed recycle mode, once through mode, SHFC-in-line static mixer in series mode, and SHFC-CST in series mode.

Abstract: A solid hollow fiber cooling crystallizer and method for crystallizing aqueous and organic solutions are provided. The solid hollow fiber crystallizer (SHFC) for carrying out cooling crystallization of inorganic/organic microsolutes/macrosolutes from solution generally includes a bundle of non-porous hollow fibers mounted within a shell where a feed solution for crystallization flows through the lumen side of the hollow fibers and a cooling solution flows through the shell side to form nuclei and subsequently crystals in the feed solution at a temperature below its saturation temperature. The solid hollow fiber crystallizer may be combined with a mixing device, such as a completely stirred tank or static mixer, to further effectuate crystallization. The solid hollow fiber crystallizer may be operated in a number of modes including feed recycle mode, once through mode, SHFC-in-line static mixer in series mode, and SHFC-CST in series mode.

Abstract: The present invention provides a method of continuous precipitation and isolation of an amorphous solid particulate form of 3-[2-(3-tert-Butyl-ureido)-3,3-dimethyl-butyryl]-6,6-dimethyl-3-aza-bicyclo[3.1.0]hexane-2-carboxylic acid (2-carbamoyl-1-cyclobutylmethyl-2-oxo-ethyl)-amide having controlled physical properties. The present invention provides also pharmaceutical formulations comprising the precipitated compound.

Abstract: The present invention provides a method of continuous precipitation and isolation of an amorphous solid particulate form of 3-[2-(3-tert-Butyl-ureido)-3,3-dimethyl-butyryl]-6,6-dimethyl-3-aza-bicyclo[3.1.0]hexane-2-carboxylic acid (2-carbamoyl-1-cyclobutylmethyl-2-oxo-ethyl)-amide having controlled physical properties. The present invention provides also pharmaceutical formulations comprising the precipitated compound.

Abstract: The present invention relates to the compound of the formula To methods of treating upper and lower obstructive airway diseases using said compound, to formulations comprising it, and to polymorphs and processes of synthesis of the polymorphic forms.

Abstract: Antisolvent crystallization systems and methods are provided that employ porous hollow fiber membranes. The porous hollow fiber membrane includes a plurality of porous hollow fibers positioned within a shell, each porous hollow fiber defining a lumen side and shell side. A crystallizing solution is introduced to one side of the hollow fibers and an antisolvent is introduced to the other side of the fibers, in either cocurrent or countercurrent flow. One of the antisolvent and the crystallizing solution permeates in part through the porous hollow fiber membrane to the other side and crystals are formed thereby. Permeation of the antisolvent or the crystallizing solution establishes advantageous radial mixing that facilitates crystal formation of a desired size distribution. Downstream mixing, e.g., a completely stirred tank or a static mixer, may be employed to further improve crystallization operations.

Abstract: Heat exchange systems are provided that include one or more polymeric hollow fibers. Exemplary hollow fibers are asymmetric and include a microporous wall and a dense skin formed thereon, thereby preventing liquid transmission and/or contamination through the wall of the hollow fiber while simultaneously enhancing heat transfer based on the presence of liquid molecules within the porous substructure of the hollow fiber. The hollow fibers may be employed in a variety of heat transfer-related commercial/industrial applications, including solvent-aqueous systems, organic-aqueous systems, organic-organic systems, desalination applications, solar heating applications, applications in the chemical industry, applications in the biomedical industry, and applications in the biotechnology or pharmaceutical industry, e.g., extracorporeal blood oxygenation systems. Heat transfer systems wherein steam is advantageously condensed on a first side of a polymeric, hollow fiber-based heat exchanger are also provided.

Abstract: A solid hollow fiber cooling crystallizer and method for crystallizing aqueous and organic solutions are provided. The solid hollow fiber crystallizer (SHFC) for carrying out cooling crystallization of inorganic/organic microsolutes/macrosolutes from solution generally includes a bundle of non-porous hollow fibers mounted within a shell where a feed solution for crystallization flows through the lumen side of the hollow fibers and a cooling solution flows through the shell side to form nuclei and subsequently crystals in the feed solution at a temperature below its saturation temperature. The solid hollow fiber crystallizer may be combined with a mixing device, such as a completely stirred tank or static mixer, to further effectuate crystallization. The solid hollow fiber crystallizer may be operated in a number of modes including feed recycle mode, once through mode, SHFC-in-line static mixer in series mode, and SHFC-CST in series mode.