Polymorphic and other crystalline forms of cis-FTC

• US 7,544,692 B2
• Filed: 04/19/2004
• Issued: 06/09/2009
• Est. Priority Date: 03/01/2001
• Status: Expired due to Term

• Current Assignee: Abbvie Incorporated
• Original Assignee: Gilead Sciences Inc.
• Inventors: Phares, Kenneth R., Hu, Yuerong, Law, Devalina
• Primary Examiner(s): Rao; Deepak
• Application Number:
  US10/827,615
• Publication Number:
  US 20050026934A1
• Time in Patent Office: 1,877 Days
• Field of Search: 544/317, 514/274
• US Class Current: 514/274
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 31/20 for DNA viruses
• CPC Class Codes: A61P 31/22 for herpes viruses
• CPC Class Codes: C07D 411/04 directly linked by a ring-member-to-ring-member bond

Abstract

Solid phases of (−)-cis-FTC, which are designated herein as amorphous (−)-FTC and Forms II and III (−)-cis-FTC) are provided that can be distinguished from Form I (−)-cis-FTC by X-ray powder diffraction patterns, thermal properties, and methods of manufacture. A hydrated crystalline form of (±)-cis-FTC (i.e. racemic cis-FTC), and a dehydrated form of the hydrate, are also provided, and can similarly be distinguished from other forms of FTC by X-ray powder diffraction patterns, thermal properties, and methods of manufacture. These FTC forms can be used in the manufacture of other forms of FTC, or in pharmaceutical compositions. Particularly preferred uses of these forms are in the treatment of HIV or hepatitis B.

Claims

1. A dehydrated crystalline form of (±

)-cis-FTC prepared by a method comprising;

a. dissolving a first crystalline form of (±

)-cis-FTC in water;

b. recrystallizing the dissolved (±

)-cis-FTC; and

c. dehydrating the recrystallized (±

)-cis-FTC;

wherein the dehydrated crystalline form of (±

)-cis-FTC is substantially in the absence of Form I (−

)-cis-FTC or substantially in the absence of hydrated crystalline (±

)-cis-FTC.

2. A pharmaceutical composition comprising a therapeutically effective amount of the crystalline form of (±

)-cis-FTC of claim 1 in combination with a pharmaceutically acceptable carrier.

3. The pharmaceutical composition of claim 2, wherein the carrier is suitable for oral delivery.

4. The pharmaceutical composition of claim 2, wherein the composition is in the form of a dosage unit.

5. The pharmaceutical composition of claim 3, wherein the (±

)-cis-FTC is present in an amount from 70-1400 mg.

6. The pharmaceutical composition of claim 3, wherein the (±

)-cis-FTC is present in an amount from 50-1000 mg.

7. The pharmaceutical composition of claim 2, wherein the composition is in the form of a tablet.

8. The pharmaceutical composition of claim 2, wherein the composition is in the form of a pill.

9. The pharmaceutical composition of claim 2, wherein the composition is in the form of a capsule.