Osteoporosis is a disease that generates progressive loss of bone mineral. The object of therapy in treatment of osteoporosis is to improve calcium absorption and decrease urinary excretion of calcium. Bisphosphonates, such as 2-(3-pyridyl)-1-hydroxyethane-1,1-bisphosphonic acid (risedronic acid), are useful in the treatment of bone diseases and calcium metabolic diseases. Particularly, Paget's disease and heterotropic ossification are being treated by ethane-1-hydroxy-1,1-bisphosphonic acid (EHDP) and risedronate sodium represented by the following formula 2 at present.

Korean Patent Application No. 10-2002-7009790 describes a selective crystallization of risedronate sodium as monohydrate (1 hydrate) or hemipentahydrate (2.5 hydrate). It discloses in that a crystalline form of monohydrate or hemipentahydrate may be selectively obtained from an aqueous solution of risedronate sodium according to the crystallization conditions, and that the crystalline form of hydrates is determined by the water and isopropanol ratio, the nucleating temperature controlled by varying the temperature, and the crystallization rate. Moreover, in the above-mentioned patent application, it discloses that the hemipentahydrate contains water in an amount of about 11.9% to about 13.9%, more preferably about 12.5% to about 13.2%, and most preferably 12.9% and is specified by various means, such as X-ray diffraction.
However, in order to selectively obtain hemipentahydrate according to the above-mentioned process, the nucleating temperature and the crystallization rate must be controlled, and particularly, a solvent in addition to purified water must be added. Thus, the process is complicated.
Further, Korean Patent Application No. 10-2006-7000683 includes the step of adjusting pH to supplement the above-mentioned patent application. However, it is disadvantageous in that the process is long and an inorganic acid must be used.
Korean Patent Application No. 10-2004-7016268 presents various hydrate forms such as A (hemipentahydrate), B, BB, B1, C, D, E, F, G, or H, a preparation method of each form, and results of X-ray diffraction, thermogravimetry analysis (TGA), and Fourier transform infrared spectroscopy (FTIR). However, the patent requires maintaining an aqueous solution of risedronate sodium at a reflux temperature, and is disadvantageous in that a solvent other than the aqueous solution of risedronate sodium must be added as in Korean Patent Application No. 10-2002-7009790.