DRUG MICROPARTICLES

• US 20100092568A1
• Filed: 12/10/2009
• Published: 04/15/2010
• Est. Priority Date: 03/26/2002
• Status: Active Grant

• Current Assignee: Anna Drabkin, Lerner E. Itzhak, Moshe Flashner-Barak, Naomi Moldavski, Vered Rosenberger
• Original Assignee: Anna Drabkin, Lerner E. Itzhak, Moshe Flashner-Barak, Naomi Moldavski, Vered Rosenberger
• Inventors: Drabkin, Anna, Flashner-Barak, Moshe, Lerner, E. Itzhak, Moldavski, Naomi, Rosenberger, Vered
• Granted Patent: US 8,663,703 B2
• Time in Patent Office: Days
• US Class Current: 424/489
• 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 at least one pharmaceutical carrier particle bearing on its surface microparticles of a poorly water soluble drug, wherein the microparticles have a mean particle size of about 100 nm to about 10 μ

m with the proviso that the poorly water soluble drug is not fenofibrate.

2. The drug delivery vehicle of claim 1, wherein the poorly water soluble drug is selected from the group consisting of itraconazole, bromocriptine, carbamazepine, diazepam, paclitaxel, etoposide, camptothecin, danazole, progesterone, nitrofurantoin, estradiol, estrone, oxfendazole, proquazone, ketoprofen, nifedipine, verapamil, and glyburide.

3. The drug delivery vehicle of claim 2 wherein the pharmaceutical carrier particle comprises at least one pharmaceutical particle selected from the group consisting of starch particles, microcrystalline starch particles, microcrystalline cellulose particles, lactose particles, and sugar particles.

4. The drug delivery vehicle of claim 3 wherein the pharmaceutical carrier particle comprises particles of microcrystalline cellulose.

5. A method of making the drug delivery vehicle of claim 1, comprising the steps of:

a) forming a solid solution comprising 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.

6. The method of claim 5 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.

7. The method of claim 5 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.

8. The method of claim 7 wherein the solvent is ethanol.

9. The method of claim 5 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.

10. The method of claim 5 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.

11. The method of claim 5 wherein the drug is selected from the group consisting of itraconazole, bromocriptine, carbamazepine, diazepam, paclitaxel, etoposide, camptothecin, danazole, progesterone, nitrofurantoin, estradiol, estrone, oxfendazole, proquazone, ketoprofen, nifedipine, verapamil, and glyburide.

12. A pharmaceutical composition comprising at least one pharmaceutically acceptable excipient and the drug delivery vehicle of claim 1.

13. An oral solid dosage form comprising a pharmaceutical composition according to claim 12.

14. The drug delivery vehicle of claim 1 wherein the ratio of carrier particles to drug is about 2:

1 to about 14;

1

15. The drug delivery vehicle of claim 14, wherein the microparticles are obtained without mechanical micronization.