Process for preparing crystalline ciclesonide with defined particle size

• US 9,422,327 B2
• Filed: 03/26/2004
• Issued: 08/23/2016
• Est. Priority Date: 03/27/2003
• Status: Active Grant

• Current Assignee: Covis Pharma GmbH (Apollo Global Management, Inc.)
• Original Assignee: Takeda GmbH (Takeda Pharmaceutical Company Limited)
• Inventors: Schmidt, Beate
• Primary Examiner(s): BASQUILL, SEAN M
• Application Number:
  US10/549,631
• Publication Number:
  US 20060128954A1
• Time in Patent Office: 4,533 Days
• US Class Current: 1/1
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 5/44 Glucocorticosteroids; Drugs increasing or potentiating the activity of glucocorticosteroids
• CPC Class Codes: C07J 71/00 Steroids in which the cyclopenta(a)hydrophenanthrene skeleton is condensed with a heterocyclic ring spiro-condensed heterocyclic rings C07J21/00, C07J33/00, C07J43/00

Abstract

The invention relates to a novel process for preparing crystalline ciclesonide with an advantageous particle size and to the use for producing pharmaceutical preparations, in particular for topical use. The crystalline ciclesonide obtained by the novel process has advantageous aerodynamic properties, and can be further processed to inhalable or nasally administered pharmaceutical preparations without further mechanical micronization.

Claims

1. A process for preparing a compound of the formula I

2. The process according to claim 1, characterized in that the suitable water-miscible organic solvent is an alcohol.

3. The process according to claim 2, characterized in that the alcohol is selected from the group consisting of methanol, ethanol, N-propanol, isopropanol and mixtures in any mixing ratio thereof.

4. The process according to claim 3, characterized in that the alcohol is ethanol.

5. The process according to claim 1, characterized in that the suitable water-miscible organic solvent is selected from the group consisting of acetone, tetrahydrofuran and dimethylformamide.

6. The process according to claim 1, characterized in that the temperature of the suitable water-miscible organic solvent is in the range from 15°

C. to 10°

C. below the boiling point of the solvent.

7. The process according to claim 6, characterized in that the temperature of the suitable water-miscible organic solvent corresponds to the room temperature at which the process is carried out.

8. The process according to claim 1, characterized in that the temperature of the water is from 10 to 50°

C.

9. The process according to claim 7, characterized in that the temperature of the water corresponds to the room temperature at which the process is carried out.

10. The process according to claim 1, characterized in that, in step (a), the compound of the formula I is substantially in the form of the R epimer.

11. The process according to claim 10, characterized in that the proportion of R epimer in the compound of the formula I is more than 95%.

12. The process according to claim 10, characterized in that the compound of the formula I is ciclesonide.

13. The process according to claim 1, characterized in that the precipitate obtained in step c) is subsequently dried.

14. The process for preparing a compound of the formula I ng to claim 1 in crystalline form with defined particle size, comprising the steps of

a) preparing a compound of the formula I by acylation of a compound of the formula II

15. The process according to claim 1, where the particle size is characterized by an X₅₀ in the range from 1.8 to 2.0.

16. The process according to claim 14, where the organic solvents used in steps b) and e) are the same solvents.