Claims
- 1. A crystalline forms of (2S,3S)-N-(methoxy-5t-butylphenylmethyl-2-diphenylmethyl-1-azobicyclo[2,2,2]octan-3-amine citrate having the formula wherein said crystalline form is a stable polymorphic Form A exhibiting the X-ray powder diffraction pattern PeakNo.1234567d13.287.707.456.345.335.064.40space.
- 2. The citrate monohydrate polymorphic form according to claim 1 wherein its crystalline habits are plates.
- 3. The citrate monohydrate polymorphic form according to claim 1 wherein the citrate monohydrate is nonhygroscopic.
- 4. The citrate monohydrate polymorphic form according to claim 1 wherein volatilization occurs at about 116° C.
- 5. The citrate monohydrate polymorph according to claim 1 wherein melt onset occurs at about 152.7° C.
- 6. A pharmaceutical composition having CNS active NK-1 receptor antagonist activity comprising the polymorphic Form according to claim 1, in an amount effective in the treatment of emesis, and a pharmaceutically acceptable carrier.
- 7. A method of treating emesis which comprises administering to a subject in need of treatment an antiemetic effective amount of the polymorphic Form A of the compound of claim 1.
- 8. A method of making the crystalline polymorphic Form of (2S,3S)-N-(methoxy-5-t-butylphenylmethyl-2-diphenylmethyl-1-azobicyclo2,2,2 octan-3-amine citrate monohydrate salt comprising:Adding citric acid to a solution of the free base, in acetone; dissolving the solid for about 2 hours; filtering and stirring the clear solution overnight; Adding filtered isopropyl ether followed by the addition of filtered water; Stirring the resulting mixture at ambient temperature until crystallization starts and granulating for an about 16 hours; and collecting the white crystalline salt formed by filtration and drying at about 45° C. under vacuum with a nitrogen purge for about 24 hours.
- 9. The method of claim 8 wherein the slurrying is carried out under ambient conditions for about 1.5 to 72 hours granulation in isopropyl ether, isopropyl alcohol and water.
- 10. The method of claim 8 wherein the citric acid is greater than 99.5% anhydrous.
Parent Case Info
The application claims the benefit of U.S. Provisional Patent Application No. 60/136,992 filed Jun. 1, 1999.
US Referenced Citations (1)
Number |
Name |
Date |
Kind |
5939433 |
Ito et al. |
Aug 1999 |
|
Non-Patent Literature Citations (2)
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Hesketh, P.J. et al. : Randomized phase II study of the Neurokinin 1 receptor antagonist CJ-11,974 in the control of Cisplatin-induced emesis. J. Clin. Oncol. vol. 17, pp. 338-343, Jan. 1999.* |
Biles, J.A. : Crystallography. Part II. J. Pharm. Sci. vol. 51, pp. 601-617, Jul. 1962. |
Provisional Applications (1)
|
Number |
Date |
Country |
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60/136992 |
Jun 1999 |
US |