Tromethamine salt of bimatoprost acid in crystalline form, methods for preparation, and methods for use thereof

Patent metadata

Field	Value
Publication number	US-9447014-B2
Application number	US-201314137447-A
Country	US
Kind code	B2
Filing date	Dec 20, 2013
Priority date	Dec 28, 2012
Publication date	Sep 20, 2016
Grant date	Sep 20, 2016

Abstract

The present invention provides tromethamine salt of 7-[3,5-Dihydroxy-2-(3-hydroxy-5-phenyl-pent-1-enyl)-cyclopentyl]-hept-5-enoic acid in crystalline and amorphous form. This compound is may also be referred to as “tromethamine salt of bimatoprost acid.” The invention crystalline form is useful for solid ocular implant or topical formulations, utilized in the treatment of various ocular conditions, such as, for example, ocular hypertension.

First claim

What is claimed is:

1. Tromethamine salt of bimatoprost acid in crystalline form having the XRPD pattern substantially as shown in FIG. 3 .

2. Tromethamine salt of bimatoprost acid in crystalline form having XRPD peaks at the diffraction angles of about: 6.8°, 10.2°, 13.4°, 16.1°, 17.3°, 18.0°, 19.1°, 19.4°, 20.0°, 20.4°, 21.1°, 22.9°, 23.3°, 24.5°, 25.2° and 33.7° of 2-theta (Cu, K-alpha radiation).

3. Tromethamine salt of bimatoprost acid in crystalline form having a melting enthalpy from about 103.6 J/g to about 119.9 J/g.

4. Tromethamine salt of bimatoprost acid in crystalline form having a melting temperature within the range of about 104-110° C.

5. Tromethamine salt of bimatoprost acid in crystalline form having a melting temperature of about 105° C.

6. Tromethamine salt of bimatoprost acid in crystalline form having a melting temperature of about 105.6° C.

7. A pharmaceutical composition comprising a therapeutically effective amount of tromethamine salt of the bimatoprost acid in crystalline form of claim 2 .

8. The pharmaceutical composition of claim 7 wherein the tromethamine salt of bimatoprost acid in crystalline form is in a pharmaceutically acceptable carrier.

9. The pharmaceutical composition of claim 8 wherein the pharmaceutically acceptable carrier is aqueous solution.

10. The pharmaceutical composition of claim 9 wherein the ophthalmically acceptable carrier is selected from the group consisting of ophthalmically acceptable diluents, buffers, hydrochloric acid, sodium hydroxide, preservatives, stabilizers, tonicity adjustors, viscosity-enhancing agents, chelating agents, surfactants and/or solubilizers and combinations thereof.

11. The pharmaceutical composition of claim 8 wherein the pharmaceutically acceptable carrier is a solid dosage form.

12. The pharmaceutical composition of claim 11 wherein the solid dosage form is an ocular implant.

13. The pharmaceutical composition of claim 7 wherein the pharmaceutical composition may be used to treat one selected from the group consisting of elevated intraocular pressure, glaucoma, localized fat reduction or promotion of hair growth.

14. The pharmaceutical composition of claim 12 wherein the solid dosage form is used to treat elevated intraocular pressure or glaucoma.

15. The pharmaceutical composition of claim 9 wherein the bimatoprost acid in crystalline form is present in a concentration of 0.01% w/v to 0.1% w/v.

16. The pharmaceutical composition of claim 9 wherein the bimatoprost acid in crystalline form is present in a concentration of 0.03% w/v.

17. A method for treating ocular hypertension comprising administering to a subject in need thereof a therapeutically effective amount of the tromethamine salt of bimatoprost acid in crystalline form of claim 2 , in an ophthalmically acceptable carrier.

18. The method of claim 17 wherein the ophthalmically acceptable carrier is selected from the group consisting of ophthalmically acceptable diluents, buffers, hydrochloric acid, sodium hydroxide, preservatives, stabilizers, tonicity adjustors, viscosity-enhancing agents, chelating agents, surfactants and/or solubilizers and combinations thereof.

19. The method of claim 17 wherein the tromethamine salt of bimatoprost acid in crystalline is dosed at least once a day.

20. The method claim 19 wherein the tromethamine salt of bimatoprost acid in crystalline form is dosed once a day.

Assignees

• Allergan Inc

Inventors

• Karami Thomas K
• Smith Scott W
• Dubas-Fisher Fiona
• St Clair Brown Adrian

Classifications

• C07C405/00

  Compounds containing a five-membered ring having two side-chains in ortho position to each other, and having oxygen atoms directly attached to the ring in ortho position to one of the side-chains, one side-chain containing, not directly attached to the ring, a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, and the other side-chain having oxygen atoms attached in gamma-position to the ring, e.g. prostaglandins {; Analogues or derivatives thereof} · CPC title

• C07C215/10 Primary

  with one amino group and at least two hydroxy groups bound to the carbon skeleton · CPC title

• C07C59/54 Primary

  containing six-membered aromatic rings and other rings · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• A61P27/06

  Antiglaucoma agents or miotics · CPC title