Method of producing polymorphic crystals of donepezil hydrochloride

A method of producing a crystalline form (III) of donepezil hydrochloride (chemical name:

• 1-benzyl-4-[(5,6-dimethoxy-1-indanon)-2-yl]methylpiperidine•monohydrochioride) represented by the following structural formula 1:
• by the steps of:
• dissolving donepezil (chemical name:
• 1-benzyl-4-[(5,6-dimethoxy-1-indanon)-2-yl]methylpiperidine) in ethanol;
• adding hydrochloric acid or hydrogen chloride thereto;
• stirring while keeping the internal temperature at 10 to 40° C.;
• and
• then collecting by filtration and drying the resulting crystals;
• wherein the crystalline form (III) of donepezil hydrochloride is a crystalline form having peaks at the following diffraction angles (2θ) in its powder X-ray diffraction patterns;
• TABLE 1
• Diffraction angle
• (2θ°)
• Intensity (I/Io)
• 6.56
• 30
• 9.94
• 8
• 13.00
• 17
• 15.00
• 47
• 15.26
• 14
• 15.74
• 6
• 16.48
• 35
• 17.42
• 4
• 18.10
• 21
• 18.50
• 56
• 19.50
• 17
• 20.10
• 32
• 20.94
• 21
• 21.66
• 100
• 22.32
• 25
• 22.92
• 17
• 23.92
• 19
• 24.68
• 17
• 26.00
• 44
• 27.20
• 23
• 28.02
• 29
• 28.22
• 40
• 28.60
• 13
• with absorption at the following wave numbers in its infrared absorption spectrum in potassium bromide:
• 559, 641, 648, 702, 749, 765, 786, 807, 851, 872, 927, 949, 966, 975, 982, 1007, 1034, 1071, 1080, 1111, 1119, 1131, 1177, 1190, 1205, 1217, 1230, 1250, 1265, 1292, 1313, 1367, 1389, 1420, 1438, 1453, 1461, 1470, 1500, 1589, 1605, 1697, 2407,2419, 2461, 2624, 2641, 2651, 2667, 2837, 2848, 2873, 2924, 2954, 2961, 2993, 3007, 3377, 3433 cm−1;
• or a crystalline form having peaks at the following diffraction angles (2θ) in its powder X-ray diffraction patterns;
• TABLE 2
• Diffraction angle
• (2θ°)
• Intensity (I/Io)
• 6.48
• 21
• 9.84
• 7
• 12.96
• 19
• 14.94
• 45
• 15.20
• 13
• 16.44
• 31
• 18.04
• 20
• 18.46
• 55
• 19.44
• 17
• 20.02
• 30
• 20.86
• 20
• 21.02
• 13
• 21.58
• 100
• 22.22
• 23
• 22.90
• 15
• 23.92
• 13
• 24.64
• 15
• 25.92
• 40
• 26.18
• 17
• 27.14
• 21
• 28.14
• 37
• 28.56
• 11
• 29.94
• 12
• with absorption at the following wave numbers in its infrared absorption spectrum in potassium bromide:
• 558.3, 641.1, 702.4, 748.5, 765.0, 786.1, 807.3, 850.8, 872.0, 926.8, 974.9, 1034.1, 1071.5, 1111.6, 1190.1, 1216.6, 1265.4, 1291.9, 1312.9, 1364.4, 1420.2, 1438.1, 1458.8, 1499.1, 1522.2, 1542.6, 1560.1, 1570.2, 1589.1, 1638.8, 1647.8, 1654.3, 1697.3, 1718.1, 1734.5, 1751.4, 1773.7, 1793.5, 1845.8, 2345.3, 2461.6, 2924.2, 3447.9 cm−1.