Stable shaped particles of crystalline organic compounds

• US 7,427,413 B2
• Filed: 02/26/2003
• Issued: 09/23/2008
• Est. Priority Date: 02/25/1998
• Status: Expired due to Fees

• Current Assignee: Skendi Finance, Ltd.
• Original Assignee: Skendi Finance, Ltd.
• Inventors: Gomez, Abraham, Savoir, John-Claude, Angeles, Juan, De Gyves, Aurelio
• Primary Examiner(s): Woodward; M P
• Assistant Examiner(s): Mercier; Melissa S
• Application Number:
  US10/372,897
• Publication Number:
  US 20040166164A1
• Time in Patent Office: 2,036 Days
• Field of Search: 424/489
• US Class Current: 424/489
• CPC Class Codes: A61K 9/1688 resulting in pure drug agglomerate optionally containing up to 5% of excipient
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 5/30 Oestrogens
• CPC Class Codes: Y10T 428/2982 Particulate matter [e.g., sphere, flake, etc.]
• CPC Class Codes: Y10T 428/2989 Microcapsule with solid core [includes liposome]

Abstract

The present invention provides storage stable, shaped particles of allotropic organic compounds. The particles of the present invention can be shaped according to the desired application. Preferred shapes of such particles are microspheres, particularly those having diameters of about 1 to about 1,000 microns. The stable shaped particles of the present invention are particularly well-suited to the fabrication of pharmaceutical formulations, particularly where sustained release and uniform bioavailability are desired. The storage stable particles are formed by a solid state crystallization of allotropic organic compounds. The solid state crystallization process of the present invention affords a means for achieving a storage stable crystalline form of said allotropic compound without loss or deterioration of the original particle dimensions.

Claims

1. A method for effecting solid state crystallization of shaped particles of allotropic organic compounds comprising:

a) creating a mixture consisting essentially of two or more allotropic organic compounds wherein each of the compounds is of mixed crystalline, amorphous, or both crystalline and amorphous form;

b) fabricating said mixture into a plurality of spherical particles;

c) exposing said spherical particles to an atmosphere containing vapors of one or more solvents for each of said allotropic organic compounds for a time sufficient to effect a solid state crystallization of each of said allotropic organic compounds to its most stable crystalline form; and

d) recovering said particles;

wherein the recovered particles retain spherical shape on storage in aqueous media for at least about one month.

2. The method of claim 1, wherein the step of fabricating said mixture into a plurality of particles of uniform shape comprises melt-congealing said mixture into a plurality of microspheres.

3. The method of claim 1, wherein said solvent is selected from the group consisting of:

water, ethanol, acetone, acetic acid, toluene, benzene, and combinations thereof.

4. The method of claim 3, wherein at least one of said allotropic organic compounds is a sterol or steroid.

5. The method of claim 4, wherein said sterol or steroid is selected from the group consisting of:

17-β

-estradiol, estrogen, testosterone, progesterone, cholesterol, and mixtures thereof.

6. The method of claim 4, wherein said formulation further comprises an allotropic organic compound selected from the group consisting of:

astemizole, cisapride, and oxatomide.

7. The method of claim 1, wherein said vapor-containing atmosphere is maintained at a temperature and pressure sufficient to effect vaporization of said solvent, but below the melting point of said organic compound.

8. The method of claim 1, wherein the uniform crystalline form of the allotropic organic compound is a hydrate.

9. The method of claim 1, wherein said spherical particles have uniform diameter between about 1 micron and about 500 microns.

10. The method of claim 1, wherein said spherical particles have varying diameter between about 1 micron and about 500 microns.