US2004034057A1PendingUtilityA1
Process for producing multiform crystal of donepezil hydrochloride
Priority: Sep 25, 2000Filed: Sep 17, 2001Published: Feb 19, 2004
Est. expirySep 25, 2020(expired)· nominal 20-yr term from priority
A61P 9/10A61P 43/00A61P 9/00A61P 25/00C07D 211/32A61P 25/28
42
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Claims
Abstract
The present invention provides a simple method of producing polymorphic crystal (III), which has high safety to environment and the bodies of operators; is gentle to environment; and can produce at low costs; and has a high refining effect. It is a method of producing polymorphic crystal (III) of donepezil hydrochloride (chemical name: 1-benzyl-4-[(5,6-dimethoxy-1-indanon)-2-yl)methylpiperidine·monohydrochloride) represented by the following structural formula (formula (I)), which comprises dissolving donepezil (chemical name: 1-benzyl-4-[(5,6-dimethoxy-1-indanon)-2-yl]methylpiperidine) in ethanol; and adding hydrochloric acid or hydrogen chloride thereto, followed by stirring.
Claims
exact text as granted — not AI-modified1 . A method of producing polymorphic crystal (III) of donepezil hydrochloride (chemical name: 1-benzyl-4-[(5,6-dimethoxy-1-indanon)-2-yl]methylpiperidine·monohydrochloride) represented by the following structural formula (formula (I)), which comprises dissolving donepezil (chemical name: 1-benzyl-4-[(5,6-dimethoxy-l-indanon)-2-yl]methylpiperidine) in ethanol; adding hydrochloric acid or hydrogen chloride thereto; and stirring.
2 . A method of producing polymorphic crystal (III) of donepezil hydrochloride, which comprises dissolving donepezil in ethanol; adding hydrochloric acid or hydrogen chloride thereto; stirring; and then collecting by filtration and drying the crystals.
3 . The method of producing polymorphic crystal (III) of donepezil hydrochloride according to claim 1 or 2 , wherein the polymorphic crystal (III) of donepezil hydrochloride is a polymorphic crystal having peaks at the following diffraction angles (2θ) in its powder X-ray diffraction patterns;
TABLE 1
Diffraction angle
(2 θ°)
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
and 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 and 3433 cm −1 , or a polymorphic crystal having peaks at the following diffraction angles (2θ) in its powder X-ray diffraction patterns;
TABLE 2
Diffraction angle
(2 θ°)
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
and 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 and 3447.9 cm −1 .
4 . The method of producing polymorphic crystal (III) of donepezil hydrochloride according to claim 1 or 2 , wherein the amount of ethanol is 3 to 20 parts by weight to one part by weight of donepezil.
5 . The method of producing polymorphic crystal (III) of donepezil hydrochloride according to claim 1 or 2 , which comprises, after adding hydrochloric acid or hydrogen chloride thereto, stirring while keeping the internal temperature at 10 to 40° C.
6 . The method of producing polymorphic crystal (III) of donepezil hydrochloride according to claim 5 , which comprises, after adding hydrochloric acid or hydrogen chloride thereto, stirring while keeping the internal temperature at 10 to 40° C.; and, after one hour passes after crystals starts precipitating, cooling to the internal temperature of 0° C. or more and less than 10° C.
7 . The method of producing polymorphic crystal (III) of donepezil hydrochloride according to claim 1 or 2 , wherein after hydrochloric acid or hydrogen chloride is added thereto, seed crystals of polymorphic crystal (III) of donepezil hydrochloride is added thereto in an amount of 0.01 to 10% by weight to the weight of donepezil.Join the waitlist — get patent alerts
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