Ibuprofen is crystallized from a .delta.H.gtoreq.8 liquid such as a C.sub.1 to C.sub.3 -alkanol, e.g., methanol, containing solutions thereof to obtain ibuprofen crystals which are equant (cube, sphere or grain) in shape, which ibuprofen crystals have larger average partile size, higher bulk density, lower bulk volume and improved flow properties compared to previously known bulk ibuprofen crystalline materials.
A process for producing crystalline ibuprofen having a crystal habit characterized by a particle length larger than 75 microns average and a length to width aspect ratio of greater than about 4 to 1 to about 5 to 1. The process involves crystallizing ibuprofen from a saturated solution of ibuprofen in a liquid hydrocarbon solvent by seeding and cooling such solution to a temperature of about 0.degree. C. to about -20.degree. C. at a rate to retard primary nucleation and promote secondary nucleation. The crystalline ibuprofen is separated from the slurry produced from such cooling.
Ibuprofen is isolated from tablets or other solids by dissolving the ibuprofen in an alkane or cycloalkane solvent, filtering off undissolved solid, and stripping the solvent from the ibuprofen by evaporation or by recrystallization at low temperatures.
This invention pertains to a method of purifying ibuprofen-comprising reaction product mixtures. The method of purification is based on crystallization of ibuprofen from a hydrocarbon solvent and the discovery that there are impurity complexes in the ibuprofen-comprising reaction product mixtures which cannot be removed by crystallization from a hydrocarbon solvent. The method of the invention includes at least one step in which the impurity complex in a first ibuprofen-comprising mixture is destabilized or broken up, followed by crystallization of the ibuprofen from a second solution or mixture comprising the first ibuprofen-comprising mixture, whereby the impurities which were previously complexed can then be removed from the ibuprofen by the crystallization of ibuprofen from a solvent.
A process for producing crystalline ibuprofen having a crystal habit characterized by a particle length larger than 75 microns average and a length to width aspect ratio of greater than about 4 to 1 to about 5 to 1. The process involves crystallizing ibuprofen from a saturated solution of ibuprofen in a liquid hydrocarbon solvent by seeding and cooling such solution to a temperature of about 0.degree. C. to about -20.degree. C. at a rate to retard primary nucleation and promote secondary nucleation. The crystalline ibuprofen is separated from the slurry produced from such cooling.
The invention relates to a process for the crystallization of substances having a narrow metastable supersaturation zone. In the process the saturation of a solution is gradually increased and the solution is seeded for the crystallization. The seeding is performed at a seeding point which is selected in response to a signal received from said process indicating imminent or initial spontaneous nucleation. The process provides a good crystal yield and a crystalline product having a uniform crystal structure and a narrow crystal size distribution.
