Drug microparticles

• US 20030224059A1
• Filed: 03/25/2003
• Published: 12/04/2003
• Est. Priority Date: 03/26/2002
• Status: Abandoned Application

• Current Assignee: Teva Pharmaceuticals USA, Inc. (Teva Pharmaceutical Industries Limited)
• Original Assignee: Teva Pharmaceuticals USA, Inc. (Teva Pharmaceutical Industries Limited)
• Inventors: Drabkin, Anna, Flashner-Barak, Moshe, Lerner, E. Itzhak, Moldavski, Naomi, Rosenberger, Vered
• Application Number:
  US10/400,100
• Publication Number:
  US 20030224059A1
• Time in Patent Office: Days
• US Class Current: 424/493
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 9/167 with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface with further drug-free outer coating A61K9/5073
• CPC Class Codes: A61K 9/1676 having a drug-free core with discrete complete coating layer containing drug adsorbates of liquid drug formulations on inert powders without simultaneous granulation step A61K9/141; with further drug-free outer coating A61K9/5078; drug conjugated to non-active particles A61K47/6921
• CPC Class Codes: A61K 9/1682 Processes
• CPC Class Codes: A61K 9/1694 resulting in granules or microspheres of the matrix type containing more than 5% of excipient
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: B01J 13/02 Making microcapsules or microballoons for medical preparations A61K9/50
• CPC Class Codes: B01J 13/125 by evaporation of the solvent apparatus therefor B01J13/043

Abstract

Provided are microparticles of active pharmaceutical ingredients, drug delivery vehicles comprising same, and methods for making them.

Claims

1. A drug delivery vehicle comprising a pharmaceutical carrier particle bearing microparticles of a drug deposited on the pharmaceutical carrier particle from a solid solution of the drug in a sublimable carrier.

2. The drug delivery vehicle of claim 1 wherein the drug is a poorly water soluble drug.

3. The drug delivery vehicle of claim 2 wherein the poorly water soluble drug is selected from the group consisting of:

fenofibrate, itraconazole, bromocriptine, carbamazepine, diazepam, paclitaxel, etoposide, camptothecin, danazole, progesterone, nitrofurantoin, estradiol, estrone, oxfendazole, proquazone, ketoprofen, nifedipine, verapamil, and glyburide.

4. The drug delivery vehicle of claim 1 wherein the sublimable carrier comprises one or more members selected from the group consisting of menthol, thymol, camphor, t-butanol, trichloro-t-butanol, imidazole, coumarin, acetic acid (glacial), dimethylsulfone, urea, vanillin, camphene, salicylamide, and 2-aminopyridine.

5. The drug delivery vehicle of claim 4 wherein the sublimable carrier is menthol.

6. The drug delivery vehicle of claim 1 wherein the pharmaceuticle carrier particle comprises at least on pharmaceutical particle selected from starch particles, microcrystalline starch particles, microcrystalline cellulose particles, lactose particles, and sugar particles.

7. The drug delivery vehilcle of claim 6 wherein the pharmaceutical carrier particle comprises particles of microcrystalline cellulose.

8. The method of claim 6 wherein the solid solution is formed by combining the drug and sublimable carrier with an organic solvent and thereafter evaporating the organic solvent to obtain the solid solution.

9. A method of making a drug delivery vehicle comprising the steps of:

a) forming a solid solution of the drug and a sublimable carrier on the surface of a pharmaceutical carrier particle, and

b) subliming the sublimable carrier from the solid solution to deposit microparticles of the drug on the surface of the pharmaceutical carrier particle to obtain the drug delivery vehicle.

10. The method of claim 9 wherein the solid solution is formed by combining the drug with molten sublimable carrier, applying the combination to at least one pharmaceutical carrier particle, and thereafter allowing the combination to solidify to obtain the solid solution on the surface of the pharmaceutical carrier particle.

11. The method of claim 9 wherein the solid solution is formed by combining the drug and the sublimable carrier with an organic solvent, applying the combination to at least one pharmaceutical carrier particle, and evaporating the organic solvent to obtain the solid solution on the surface of the at least one pharmaceutical carrier particle.

12. The method of claim 11 wherein the solvent is ethanol.

13. The method of claim 9 wherein the drug is selected from the group consisting of fenofibrate, itraconazole, bromocriptine, carbamazepine, diazepam, paclitaxel, etoposide, camptothecin, danazole, progesterone, nitrofurantoin, estradiol, estrone, oxfendazole, proquazone, ketoprofen, nifedipine, verapamil, and glyburide.

14. The method of claim 9 wherein the sublimable carrier is selected from the group consisting of menthol, thymol, camphor, t-butanol, trichloro-t-butanol, imidazole, coumarin, acetic acid (glacial), dimethylsulfone, urea, vanillin, camphene, salicylamide, and 2-aminopyridine.

15. The method of claim 9 wherein the pharmaceutical carrier particle is selected from the group consisting of starch particles, sugar particles, lactose particles, particles of microcrystalline cellulose, and mixtures of any of these.

16. The method of claim 9 wherein the sublimable carrier is sublimed from the solid solution by treating the pharmaceitical carrier particles in a fludized bed drier at a temperature below the melting point of the solid solution.

20. An oral solid dosage form comprising a pharmaceutical composition according to claim 16.

17. A pharmaceutical composition comprising a plurality of microparticles of a drug and at least one pharmaceutically acceptable excipient, wherein the microparticles are formed by removing sublimable carrier from a solid solution of the drug in the sublimable carrier.

18. The pharmaceutical composition of claim 17 wherein the solid solution is formed on the surface of a plurality of pharmaceutical carrier particle.

19. The pharmaceutical composition of claim 17 wherein the sublimable carrier is removed from the solid solution that is on the surfaces of the plurality of pharmaceutical carrier particles, whereby the plurality of microparticles are born by the plurality of pharmaceutical carrier particles.