Enteric coated bead comprising ixabepilone, and preparation and administration thereof

• US 20060153917A1
• Filed: 11/17/2005
• Published: 07/13/2006
• Est. Priority Date: 11/18/2004
• Status: Abandoned Application

• Current Assignee: Bristol-Myers Squibb Company
• Original Assignee: Bristol-Myers Squibb Company
• Inventors: Ullah, Ismat, Wiley, Gary James
• Application Number:
  US11/281,855
• Publication Number:
  US 20060153917A1
• Time in Patent Office: Days
• US Class Current: 424/470
• CPC Class Codes: A61K 31/427 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 9/5078 with drug-free core
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 29/02 without antiinflammatory effect
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

Disclosed is an enteric coated bead comprising Ixabepilone, a compound having a structure Also disclosed is a capsule comprising a multitude of the enteric coated beads. Further, a method of preparing the enteric coated bead and a method of treating cancer or other proliferative diseases using the enteric coated bead are disclosed.

Claims

1. An enteric coated bead comprising:

a) coated particle comprising;

i) a base particle; and

ii) an active ingredient layer disposed on said base particle, wherein said active ingredient layer comprises;

1) a compound having the formula

or a pharmaceutically acceptable salt, solvate, clathrate, hydrate, or prodrug thereof; and

2) at least one binder; and

b) an enteric coating encapsulating said coated particle.

2. The enteric coated bead according to claim 1 comprising, based on weight of said enteric coated bead,

a) from about 10 to about 80 weight % of said base particle;

b) from about 0.1 to about 50 weight % of said active ingredient layer; and

c) from about 5 to about 55 weight % of said enteric coating.

3. The enteric coated bead according to claim 1, wherein said enteric coated bead is substantially free of moisture.

4. The enteric coated bead according to claim 1 wherein said at least one binder is starch, gelatin, sucrose, glucose, dextrose, molasses, modified dextrins, lactose, acacia, sodium alginate, potassium alginate, methyl cellulose, hydroxymethyl cellulose, hydroxypropyl methylcellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, guar gum, xanthan gum, polyvinylpyrrolidone, poly(vinylpyrrolidone-vinyl acetate) copolymers, or a mixture thereof.

5. The enteric coated bead according to claim 1 wherein said enteric coating comprises hydroxypropyl methylcellulose phthalate, polyvinyl acetate phthalate, cellulose acetate phthalate, hydroxypropyl methylcellulose acetate succinate, or methacrylic acid copolymer.

6. The enteric coated bead according to claim 1 further comprising a subcoat layer interposed between said active ingredient layer and said enteric coating.

7. The enteric coated bead according to claim 6 comprising from about 0.1 to about 10 weight % of said subcoat layer, based on weight of said enteric coated bead.

8. The enteric coated bead according to claim 6 wherein said subcoat layer is starch, gelatin, sucrose, glucose, dextrose, molasses, modified dextrins, lactose, acacia, sodium alginate, potassium alginate, methyl cellulose, hydroxymethyl cellulose, hydroxypropyl methylcellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, guar gum, xanthan gum, polyvinylpyrrolidone, poly(vinylpyrrolidone-vinyl acetate) copolymers, or a mixture thereof.

9. The enteric coated bead according to claim 1 having a diameter in the range of from about 0.5 millimeter to about 7 millimeters.

10. A capsule comprising enteric coated beads according to claim 1.

11. The capsule according to claim 10 further comprising at least one hydrophobic material selected from talc, magnesium stearate, stearic acid, glyceryl behenate, hydrogenated cottonseed oil, trimyristin, triplamitan, tristearin, and fumed silica.

20. A method of treating cancer or other proliferative diseases in a mammal, comprising:

administering orally an effective amount of at least one enteric coated bead of claim 1.

21. The method according to claim 20 wherein said mammal is human and said effective amount is in a range of from about 1 to about 500 mg/m² of said compound, or a pharmaceutically acceptable salt, solvate, clathrate, hydrate, or prodrug thereof.

22. The method according to claim 20 wherein said cancer is breast cancer or lung cancer.

23. The method according to claim 20 comprising administering orally a capsule comprising a multitude of said coated beads.

12. A process for preparing enteric coated beads, comprising:

a) providing base particles;

b) applying an active ingredient mixture and binder to said base particles, wherein said active ingredient mixture comprises

i) a compound having the structure;

or a pharmaceutically acceptable salt, solvate, clathrate, hydrate, or prodrug thereof, and

ii) solvent, water, or a mixture thereof;

c) drying said base particles having application of said active ingredient mixture to provide coated particles; and

d) applying an enteric coating to said coated particles to provide said enteric coated beads.

13. The process according to claim 12 wherein said active ingredient mixture is an aqueous active ingredient suspension comprising particles of said compound in water.

14. The process according to claim 13 wherein said aqueous active ingredient suspension has a pH in the range of from about 6 to about 9.

15. The process according to claim 14 wherein said aqueous active ingredient suspension further comprises buffer.

16. The process according to claim 13 wherein said aqueous active ingredient suspension is applied to said base particles in step b) by spraying in a fluid bed spraying apparatus.

17. The process according to claim 16 wherein said base particles having application of said aqueous active ingredient suspension are dried in step c) at a temperature in the range of from about 25°

C. to about 35°

C. in said fluid bed spraying apparatus.

18. The process according to claim 12 wherein said enteric coated bead is substantially free of moisture.

19. The process according to claim 12 wherein said base particles in step a) are substantially free of moisture.