INTRODUCTION:
Present invention relates to novel crystalline forms of risedronate monosodium, process for their preparation and pharmaceutical compositions containing them.
Patent EP Appl. 186,405 describes preparation of risedronic acid and its monosodium salt useful as bone resorption inhibitor. Risedronic acid monosodium is sodium [1-hydroxy-2-(3-pyridinyl)ethylidene]bisphosphonate of the formula-I.

The aforesaid European patent describes the preparation of risedronate by bisphosphonylation of 3-pyridinylacetic acid using phosphorous trichloride and phosphorous acid. The resultant risedronic acid is converted to its monosodium using sodium hydroxide.
BACKGROUND OF INVENTION:
In the PCT application WO 03/086355 a number of polymorphs and pseudopolymorphs are disclosed for risedronate sodium. These forms are named as Form A, B, BB, Bl, C, D, E, F5 G, H. Process for preparation of these forms and thermal stability, inter conversion of these forms are also discussed in this patent application.
During the risedronate monosodium salt formation we observed three novel crystalline forms which are different from all the previously known forms of risedronate monosodium. These novel forms are found to be stable, reproducible, and suitable for pharmaceutical preparations.
Accordingly the main objective of the present invention is to provide three stable and novel crystalline forms of risedronate monosodium, process for the preparation of said

novel crystalline forms and pharmaceutical compositions containing these novel crystalline forms.
DESCRIPTION OF THE INVENTION:
According to one aspect of the present invention there is provided a novel crystalline form of risedronate monosodium, designated as Form I, characterized by an X-ray powder diffraction pattern having peaks expressed as 2G (intensity in %) 9.06 (8.4), 12.35 (100), 13.00 (2J), 23.73 (2.7), 24.03 (2.6), 24.72 (35.3), and 31.26 (3.2) degrees. IR (KBr) spectrum of Form I is having peaks at 3370, 3096, 1655, 1569, 1478, 1436, 1387, 1320, 1213, 1133, 1073, 1032, 935, 890, 800, 742, 687, 660, 629, 604, 535, and 472cm"1.
According to another aspect of the present invention there is provided a process for preparation of Form I of risedronate monosodium. Thus, risedronic acid of formula-II is suspended in water and added aqueous sodium hydroxide and heated to get a clear solution. Cooling of this solution to 5-10°C gave crude risederonate monosodium crystals. The crude risedronate monosodium was recrystallized from aqueous methanol and the product isolated at 5-10°C to get Form I crystals of risedronate monosodium.
According to another aspect of the present invention there is provided a novel crystalline form of risedronate monosodium, designated as Form II, characterized by an X-ray powder diffraction pattern having peaks expressed as 20 (intensity in %) 6.09 (93.8), 9.08 (100), 12.1 (14.2), 12.34 (45.2), 13.03 (9.4), 14.44 (9.1), 15.85 (10.8), 16.68 (8.3), 17.26 (8.5), 19.15 (5.0), 19.87 (13.6), 20.65 (5.2), 21.97 (6.6), 23.02 (14.6), 23.71 (28.8), 25.60 (7.4), 27.87 (14.6), 30.41 (10.8), 31.27 (15.5), 31.86 (9.7), 35.50 (7.4), 36.61 (14.4), and 37.88 (6.4) degrees. IR (KBr) spectrum of Form II is having peaks at 3569, 3373, 1654, 1569, 1478, 1436, 1388, 1320, 1210, 1135, 1081, 1048, 986, 935, 887, 859, 818, 798, 746, 691, 660, 627, 606, 542, and 465cm-1.
According to another aspect of the present invention there is provided a process for preparation of Form II of risedronate monosodium. Thus, risedronic acid of formula-II is

suspended in water and added aqueous sodium hydroxide solution and heated to 60-70°C to get a clear solution. Ethanol was added to the solution and allowed to crystallize. The crystals were filtered at room temperature and dried to get Form II crystals of risedronate monosodium.
According to another aspect of the present invention there is provided a novel crystalline form of risedronate monosodium, designated as Form III, characterized by an X-ray powder diffraction pattern having peaks expressed as 20 (intensity in %) 8.97 (100), 12.22 (43.6), 12.92 (7.8), 15.73 (9.5), 19.81 (6.7), 22.92 (10.8), 23.60 (5.4), 23.92 (10.6), 24.58 (32.9), 26.00 (5.2), 27.85 (13.5), 31.16 (16.3), 32.77 (5.0), and 36.49 (10.5) degrees. IR (KBr) spectrum of Form III is having peaks at 3620, 3361, 3096, 1654, 1569, 1478, 1436, 1387, 1319, 1212, 1133, 1074, 1033, 935, 890, 818, 801, 745, 688, 660, 630, 604, 566, 537, and 472cm'1.
According to another aspect of the present invention there is provided a process for preparation of Form III of risedronate monosodium. Thus, risedronic acid of formula-II is suspended in water and added aqueous sodium hydroxide solution to get a clear solution at 60-70°C. The resultant solution was diluted with tetrahydrofuran to get the crystals of risedronate monosodium which were filtered at room temperature and dried to give Form III risedronate
X-ray powder diffraction spectra were measured on a Siemens D5000 x-ray powder diffractometer having a copper-Ka radiation (1.5406A). IR spectra were recorded on a Perkin Elmer FT IR instrument Model Paragon 1000.
Fig.l Powder XRD of Form-I crystals of risedronate monosodium Fig.2 IR spectrum of Form-I crystals of risedronate monosodium Fig.3 Powder XRD of Form-II crystals of risedronate monosodium Fig.4 IR spectrum of Form-II crystals of risedronate monosodium Fig.5 Powder XRD of Form-Ill crystals of risedronate monosodium Fig.6 IR spectrum of Form-Ill crystals of risedronate monosodium

The details of the process of the invention are provided in the Examples given below which are provided by way of illustration only and therefore should not be construed to limit the scope of the invention.
Examples
Example 1
Risedronate sodium (20g) and water (100ml) were taken into a flask and heated to 80-85°C to get a clear solution. The solution was slowly allowed to reach 30°C. After reaching 50°C crystallization began. Methanol (100ml) was added to the reaction mass and cooled the reaction mass to 5-10°C. After stirring the mass at 5-10°C for L5h reaction mass was filtered and washed the wet material with 2 x 15ml of 50% aqueous methanol. The wet material was dried to get 19.1g of risedronate monsodium Form-I crystals.
Example 2
Risedronic acid (5g) and water (30ml) were charged into a flask and aqueous sodium hydroxide (0.7g in 7ml of water) was added at 30°C. The reaction mass was heated to 70°C to get a clear solution. The reaction mass was filtered and ethanol (25ml) was added to the filtrate at 40-45°C. After allowing the mass to reach 30°C it was maintained for lhr at 30°C. The reaction mass was filtered and the the wet solid washed with 2 x 5ml of 50% aqueous ethanol. Drying of the solid gave 4.7g of risedronate monosodium Form-II crystals.
Example 3
Risedronic acid (5g) and water (30ml) were charged into a flask. Aqueous sodium hydroxide (0.7g in 7ml of water) was added to the reaction mass and heated to 70°C. to the resultant clear solution tetrahydroflxran (25ml) was adeed at 40-45 °C. The reaction mass was allowed to reach 30°C and maintained there for Ih before filtration. The wet

solid was washed with 2 x 5ml of 50% aqueous tetrahydrofuran. Drying of the product yielded 4.8g of Form-Ill crystals of risedronate monosodium.
Advantages of present invention:
1. Present invention provides three novel crystalline forms designated as Form I, Form II, and Form III of risedronate monosodium, which are stable, reproducible, and suitable for pharmaceutical preparations.
2. Present invention provides processes for the novel crystalline forms, namely Form I, Form II, and Form III of risedronate monosodium, which are simple and easy to adopt on a commercial scale.

WE Claims:
1. A novel crystalline form of risedronate monosodium designated as Form I, characterized by an X-ray powder diffraction pattern having peaks expressed as 20 (intensity in %) at about 9.06 (8.4), 12.35 (100), 13.00 (2.1), 23.73 (2.7), 24.03 (2.6), 24.72 (35.3), and 31.26 (3.2) degrees and the IR (KBr) spectrum having peaks at 3370, 3096, 1655, 1569, 1478, 1436, 1387, 1320, 1213, 1133, 1073, 1032, 935, 890, 800, 742, 687, 660, 629, 604, 535, and 472cm'1.
2. A novel crystalline form of risedronate monosodium, designated as Form II, characterized by an X-ray powder diffraction pattern having peaks expressed as 20 (intensity in %) at about 6.09 (93.8), 9.08 (100), 12.1 (14.2), 12.34 (45.2), 13.03 (9.4), 14.44 (9.1), 15.85 (10.8), 16.68 (8.3), 17.26 (8.5), 19.15 (5.0), 19.87 (13.6), 20.65 (5.2), 21.97 (6.6), 23.02 (14.6), 23.71 (28.8), 25.60 (7.4), 27.87 (14.6), 30.41 (10.8), 31.27 (15.5), 31.86 (9.7), 35.50 (7.4), 36.61 (14.4), and 37.88 (6.4) degrees and the IR (KBr) spectrum having peaks at 3569, 3373, 1654, 1569, 1478, 1436, 1388, 1320, 1210, 1135, 1081, 1048, 986, 935, 887, 859, 818, 798, 746, 691, 660, 627, 606, 542, and 465cm"1.
3. A novel crystalline form of risedronate monosodium, designated as Form III, characterized by an X-ray powder diffraction pattern having peaks expressed as 20 (intensity in %) at about 8.97 (100), 12.22 (43.6), 12.92 (7.8), 15.73 (9.5), 19.81 (6.7), 22.92 (10.8), 23.60 (5.4), 23.92 (10.6), 24.58 (32.9), 26.00 (5.2), 27.85 (13.5), 31.16 (16.3), 32.77 (5.0), and 36.49 (10.5) degrees and the IR (KBr) spectrum having peaks at 3620, 3361, 3096, 1654, 1569, 1478, 1436, 1387, 1319, 1212, 1133, 1074, 1033, 935, 890, 818, 801, 745, 688, 660, 630, 604, 566, 537, and 472cm"1.
4. A process for the preparation of Form I crystals of risedronate monosodium as defined
in claim 1 comprising of dissolving risedronate monosodium in water and diluting it with
methanol and isolating the Form-I crystals at 5-10°C.

5. A process for the preparation of Form II crystals of risedronate monosodium as defined in claim 2 comprising of dissolving risedronate monosodium in water and diluting it with ethanol and isolating the Form-II crystals at 25-30°C.
6. A process for the preparation of Form III crystals of risedronate monosodium as defined in claim 3 comprising of dissolving risedronate monosodium in water and diluting it with tetrahydrofuran and isolating the Form-Ill crystals at 25-30°C.
7. A pharmaceutical composition comprising the crystalline Form I of risedronate
monosodium as defined in claim 1 and a pharmaceutically acceptable carrier.
8. A pharmaceutical composition comprising the crystalline Form II of risedronate
monosodium as defined in claim 8 and a pharmaceutically acceptable carrier.
9. A pharmaceutical composition comprising the crystalline Form III of risedronate
monosodium as defined in claim 15 and a pharmaceutically acceptable carrier.