Method for the production of crystalline forms and crystalline forms of optical enantiomers of modafinil

• US 7,132,570 B2
• Filed: 12/18/2003
• Issued: 11/07/2006
• Est. Priority Date: 12/20/2002
• Status: Expired due to Fees

• Current Assignee: Teva Sante SAS (Teva Pharmaceutical Industries Limited)
• Original Assignee: Cephalon France (Teva Pharmaceutical Industries Limited)
• Inventors: Neckebrock, Olivier, Leproust, Pierre
• Primary Examiner(s): Kumar, Shailendra
• Application Number:
  US10/539,918
• Publication Number:
  US 20060135621A1
• Time in Patent Office: 1,055 Days
• Field of Search: 564/162, 514/618
• US Class Current: 564/162
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/14 Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
• CPC Class Codes: A61P 11/16 Central respiratory analeptics
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 25/22 Anxiolytics
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 25/26 Psychostimulants, e.g. nicotine, cocaine
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/02 Nutrients, e.g. vitamins, minerals
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07B 2200/07 Optical isomers
• CPC Class Codes: C07B 2200/13 Crystalline forms, e.g. polymorphs
• CPC Class Codes: C07C 315/04 by reactions not involving the formation of sulfone or sulfoxide groups
• CPC Class Codes: C07C 315/06 Separation; Purification; Stabilisation; Use of additives
• CPC Class Codes: C07C 317/28 : with sulfone or sulfoxide groups bound to acyclic carbon atoms of the carbon skeleton
• CPC Class Codes: C07C 317/44 : having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton

Abstract

The invention relates to a process for the preparation of crystalline forms of the optical enantiomers of modafinil, comprising stages comprising:

• • i) dissolving one of the optical enantiomers of modafinil in a solvent other than ethanol,
  • ii) crystallising the modafinil enantiomer,
  • iii) recovering the crystalline form of the modafinil enantiomer so obtained.

The invention also relates to a process for the preparation of the optical enantiomers of modafinil.

Claims

1. A laevorotatory enantiomer of modafinil in a polymorphic form that produces a powder X-ray diffraction spectrum comprising intensity peaks at the interplanar spacings:

8.54, 4.27, 4.02, 3.98 (Å

).

2. The laevorotatory enantiomer of modafinil according to claim 1, wherein the polymorphic form produces a powder X-ray diffraction spectrum further comprising intensity peaks at the interplanar spacings:

13.40, 6.34, 5.01, 4.68, 4.62, 4.44, 4.20, 4.15, 3.90, 3.80, 3.43 (Å

).

5. A pharmaceutical composition comprising a laevorotatory enantiomer of modafinil according to any one of claims 1 to 4.

6. A pharmaceutical composition consisting essentially of a laevorotatory enantiomer of modafinil according to according to any one of claims 1 to 4.

3. A laevorotatory enantiomer of modafinil in a polymorphic form that produces a powder X-ray diffraction spectrum comprising reflections at 15.4, 31.1, 33.1 and 33.4 degrees 2θ

.

4. The laevorotatory enantiomer of modafinil according to claim 3, wherein the polymorphic form produces a powder X-ray diffraction spectrum further comprising reflections at 9.8, 20.8, 26.4, 28.3, 28.7, 29.9, 31.6, 32, 34.1, 35.1 and 39 degrees 2θ

.

7. A Form I polymorph of (−

)-modafinil.

8. A pharmaceutical composition comprising a Form I polymorph of (−

)-modafinil according to claim 7.

9. A pharmaceutical composition consisting essentially of a Form I polymorph of (−

)-modafinil according to claim 7.

10. A process for preparing a Form I polymorph of (−

)-modafinil comprising the steps of;

(a) providing a solution of (−

)-modafinil dissolved in a hot solvent;

(b) rapidly cooling the solution from step (a) to produce crystals;

(c) filtering the crystals;

(d) drying the crystals; and

(e) obtaining the crystals of said Form I polymorph of (−

)-modafinil, wherein the solvent of step (a) is selected from water, methanol, absolute ethanol, absolute ethanol plus 3% water (v/v), and ethanol denatured with toluene plus 3% water, (v/v, based on the total volume of ethanol and toluene).