Stable shaped particles of crystalline organic compounds

• US 6,737,081 B2
• Filed: 02/26/2003
• Issued: 05/18/2004
• Est. Priority Date: 02/25/1998
• Status: Expired due to Term

• Current Assignee: Skendi Finance, Ltd.
• Original Assignee: Abraham Gomez, Aurelio D.E. Gyves, John-Claude Savoir, Juan Angeles
• Inventors: Gomez, Abraham, Savoir, John-Claude, Angeles, Juan, De Gyves, Aurelio
• Primary Examiner(s): Kishore, Gollamudi S.
• Assistant Examiner(s): Pulliam, Amy E
• Application Number:
  US10/373,088
• Publication Number:
  US 20030191101A1
• Time in Patent Office: 447 Days
• Field of Search: 424/408, 424/439, 424/451, 424/457, 424/458, 424/465, 424/469, 424/470, 424/489, 428/402, 428/402.24
• 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 a solid state crystallization of an allotropic molecular organic compound in a particle of uniform size and shape comprising:

a. creating a formulation comprising a pharmacotherapeutic molecular allotropic organic compound in a mixed crystalline, amorphous, or both crystalline and amorphous forms;

b. melt congealing said formulation into a plurality of particles of uniform shape;

c. exposing said microspheres to an atmosphere saturated with vapors of a solvent for said allotropic organic compound for a time sufficient to effect a solid state crystallization of said particles; and

d. recovering said crystallized particles,

wherein said allotropic organic compound in said recovered particles is of a uniform crystalline structure, said recovered particles have the same shape as the melt congealed particles of step (b), and said particles retain said same shape on storage in aqueous media for at least about one month.

2. The method of claim 1, wherein said particles are fabricated as microspheres of uniform diameter of between about 1 and about 1,000 microns.

3. The method of claim 1, wherein said particles are fabricated as microspheres of uniform diameter of between about 10 and about 300 microns.

4. The method of claim 1, wherein said allotropic organic compound is a sterol or steroid.

5. The method of claim 1, 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 1, wherein the allotropic organic compound is selected from the group consisting of:

astemizole, cisapride, and oxatomide.