USRE39087EExpiredUtility
Azithromycin monohydrate isopropanol clathrate and methods for the manufacture thereof
Est. expiryAug 21, 2018(expired)· nominal 20-yr term from priority
C07H 17/08
70
PatentIndex Score
3
Cited by
17
References
42
Claims
Abstract
A novel form of azithromycin and processes for preparation of pure azithromycin monohydrate isopropanol clathrate (3 molecules of isopropanol for every 10 molecules of azithromycin monohydrate) has been obtained. Preparation of the novel form of azithromycin comprises the steps of dissolving azithromycin in isopropanol, followed by the slow addition of water to the organic solution.
Claims
exact text as granted — not AI-modified1. A compound of formula II:
2. A process for the preparation of azithromycin monohydrate isopropanol clathrate which comprises the steps of:
(a) dissolving azithromycin in isopropanol and slowly adding water to the resulting solution so that a precipitate of crystalline azithromycin monohydrate isopropanol clathrate is formed;
(b) filtering and washing the product resulting from step (a) with a mixture of isopropanol and water; and
(c) vacuum drying the product resulting from step (b).
3. The process of claim 2 wherein the dissolution of crystalline azithromycin is carved out in a volume of solvent only sufficient to dissolve the azithromycin.
4. The process of claim 2 wherein water is added over a period of one hour.
5. The process of claim 2 wherein the addition of water to the resulting solution is carried out between 0° C. to 30° C.
6. The process of claim 5 wherein the addition of water is carried between 15° C. to 25° C.
7. The process of claim 2 wherein vacuum drying is carried out at a temperature of 50° C. to 60° C.
8. The process of claim 2 wherein the vacuum drying is carried out under 6 to 10 mm Hg.
9. A process for the preparation of azithromycin monohydrate isopropanol clathrate characterised by the following x-ray powder diffraction pattern expressed in terms of “D” spacings and Relative Intensity:
Relative Intensity Angle (°2θ) D-value (Å) % 4.985 17.712 0.2 5.605 15.754 0.3 6.205 14.232 1.3 7.350 12.017 1.7 7.835 11.246 7.5 8.247 10.721 0.4 8.830 10.006 0.3 9.400 9.401 4.1 9.790 9.027 100.0 10.245 6.627 0.4 11.165 7.918 8.8 11.365 7.779 2.5 11.935 7.409 1.4 12.495 7.078 4.3 13.055 6.341 2.2 14.250 6.210 1.2 14.645 6.044 2.6 14.810 3.977 1.8 15.270 5.798 3.3 15.700 5.640 2.9 15.990 5.338 0.9 16.595 5.338 1.1 17.040 5.199 2.1 17.450 5.078 1.5 18.035 4.915 0.5 18.375 4.824 1.0 18.540 4.782 1.0 19.060 4.613 2.8 19.670 4.510 2.8 19.995 4.437 1.7 20.425 4.315 2.7 20.885 4.150 1.1 21.030 4.221 0.8 21.740 4.085 0.8 22.540 3.941 0.8 23.470 3.787 0.5 24.125 3.680 0.6 24.475 3.634 0.7 24.705 3.601 0.7 25.245 3.525 0.6 25.510 3.489 0.9 26.145 1.406 0.8 26.510 3.360 0.2 28.320 3.145 0.3 29.200 3.056 0.3 29.410 3.035 0.3 29.825 2.993 0.2 32.750 2.732 0.4 33.565 2.668 0.4 34.640 2.587 0.2 35.295 2.541 0.3 36.133 2.484 0.3 37.490 2.397 0.2 39.710 2.268 0.2
which comprises the steps of:
(a) dissolving azithromycin in isopropanol and slowly adding water to the resulting solution so that a precipitate of crystalline azithromycin monohydrate isopropanol clathrate is formed;
(b) filtering and washing the product resulting from step (a) with a mixture of isopropanol and water; and
(c) vacuum drying the product resulting from step (b).
10. The compound of claim 1 which is pure.
11. The compound of claim 10 which is free of azithromycin dihydrate.
12. The compound of claim 1 formulated as a drug product.
13. The compound of claim 12 in tablet form.
14. The compound of claim 12 in capsule form.
15. Crystalline azithromycin monohydrate isopropanol clathrate.
16. The compound of claim 15 which is pure.
17. The compound of claim 16 which is free of azithromycin dihydrate.
18. The compound of claim 15 formulated as a drug product.
19. The compound of claim 18 in tablet form.
20. The compound of claim 18 in capsule form.
21. Azithromycin monohydrate isopropanol clathrate characterized by the x-ray diffraction pattern as illustrated in FIG. 3.
22. The compound of claim 21 which is pure.
23. The compound of claim 22 which is free of azithromycin dihydrate.
24. The compound of claim 21 formulated as a drug product.
25. The compound of claim 24 in tablet form.
26. The compound of claim 24 in capsule form.
27. The compound of claim 21 wherein the DSC thereof is illustrated in FIG. 6.
28. The compound of claim 21 further characterized by the IR spectrum thereof as illustrated in FIG. 7
29. The compound of claim 28 further characterized by the DSC thereof illustrated in FIG. 6.
30. Azithromycin monohydrate isopropanol clathrate characterized by the IR spectrum thereof as illustrated in FIG. 7.
31. The compound of claim 30 wherein the DSC thereof is illustrated in FIG. 6.
32. The compound of claim 30 which is pure.
33. The compound of claim 32 which is free of azithromycin dihydrate.
34. The compound of claim 30 formulated as a drug product.
35. The compound of claim 34 in tablet form.
36. The compound of claim 34 in capsule form.
37. Azithromycin monohydrate isopropanol clathrate characterized by the following x-ray powder diffraction pattern expressed in terms of “D” spacings and Relative Intensity:
Relative Intensity Angle (°2θ) D-value (Å) % 4.986 17.712 0.2 5.605 15.754 0.3 6.205 14.232 1.3 7.350 12.017 1.7 7.855 11.246 7.5 8.240 10.721 0.4 8.830 10.006 0.3 9.400 9.401 4.1 9.790 9.017 100.0 10.245 4.827 0.4 11.165 7.918 8.8 11.368 7.779 2.5 11.938 7.409 1.4 12.485 7.078 4.3 13.935 6.941 2.2 14.250 6.210 2.3 14.545 6.044 2.6 14.810 1.977 1.8 15.270 5.640 1.9 16.595 1.378 1.1 17.040 5.199 2.1 17.450 5.078 2.5 18.375 4.284 1.0 18.340 4.782 1.0 19.080 4.510 2.8 19.995 4.437 1.9 20.425 4.349 2.7 20.889 4.150 1.1 21.050 4.321 0.8 21.740 4.085 0.8 22.540 3.941 0.8 23.470 3.787 0.5 24.475 1.634 0.7 24.705 3.801 0.7 25.245 3.525 0.4 25.510 1.489 0.9 25.149 3.406 0.8 26.510 3.360 0.3 28.320 3.145 0.3 29.200 3.096 0.3 29.410 3.039 0.3 29.829 2.993 0.2 30.170 2.960 0.2 32.150 2.732 0.4 33.365 2.668 0.4 34.640 2.587 0.3 35.291 2.541 0.3 36.135 2.484 0.3 37.490 2.397 0.2 39.710 2.268 0.2.
38. The compound of claim 37 which is pure.
39. The compound of claim 38 which is free of azithromycin dihydrate.
40. The compound of claim 37 formulated as a drug product.
41. The compound of claim 40 in tablet form.
42. The drug product of claim 40 in capsule form.Cited by (0)
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