7-[3,5-dihydroxy-2- (3-hydroxy-5-phenyl-pent-1-enyl)-cyclopentyl]-N-ethyl-hept-5-enamide (bimatoprost) in crystalline form II, methods for preparation, and methods for use thereof

• US 8,629,185 B2
• Filed: 11/22/2010
• Issued: 01/14/2014
• Est. Priority Date: 11/23/2009
• Status: Active Grant

• Current Assignee: Allergan Incorporated (Abbvie Incorporated)
• Original Assignee: Allergan Incorporated (Abbvie Incorporated)
• Inventors: Ambrus, Gyorgy F., Karami, Kiomars, Wu, Ke
• Primary Examiner(s): Padmanabhan, Sreeni
• Assistant Examiner(s): Neagu, Irina
• Application Number:
  US12/951,780
• Publication Number:
  US 20110152376A1
• Time in Patent Office: 1,149 Days
• Field of Search: 514/622, 564/171
• US Class Current: 514/622
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• CPC Class Codes: A61P 9/12 Antihypertensives
• CPC Class Codes: C07C 235/30 the carbon skeleton being unsaturated and containing rings other than six-membered aromatic rings
• CPC Class Codes: C07C 235/34 having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
• CPC Class Codes: C07C 2601/08 the ring being saturated
• CPC Class Codes: C07C 405/00 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

Abstract

The present invention provides a new crystalline form of bimatoprost, designated as crystalline form II. This new crystalline form is the most stable form known to date of bimatoprost. Moreover, it has been found that bimatoprost crystalline form II is readily prepared from crystalline form I.

Claims

1. 7-[3,5-dihydroxy-2-(3-hydroxy-5-phenyl-pent-1-enyl)-cyclopentyl]-N-ethyl-hept-5-enamide having the structure

3. The crystalline form of claim 1 having the X-ray diffraction pattern as shown in FIG. 2.

4. The crystalline form of claim 1 having an endothermic onset at about 70.9 °

C. and a peak at 74.5 °

C. in its differential scanning calorimetry profile.

5. The crystalline form of claim 1 having the DSC profile as shown in FIG. 1.

7. The crystalline form of claim 1 free of other crystalline forms.

2. A crystalline form of 7-[3,5-dihydroxy-2- (3-hydroxy-5-phenyl-pent-1-enyl)- cyclopentyl]-N-ethyl-hept-5-enamide having an X-ray powder diffraction pattern with peaks at (2θ

);

3.60, 5.31, 7.09, 10.55, 12.24, 13.29, 14.55, 15.85, 17.60, 18.49, 19.00, 19.65, 21.10, 22.20, 22.69, 24.75 and 28.65.

6. A pharmaceutical composition comprising a therapeutically effective amount of 7-[3,5-dihydroxy-2-(3-hydroxy-5-phenyl-pent-1-enyl)-cyclopentyl]-N-ethyl-hept-5-enamide crystalline form II in an ophthalmically acceptable carrier therefore.