Method and composition to improve absorption of therapeutic agents

• US 20130122098A1
• Filed: 11/14/2011
• Published: 05/16/2013
• Est. Priority Date: 11/14/2011
• Status: Abandoned Application

• Current Assignee: Bayer Healthcare LLC (Bayer AG)
• Original Assignee: Bayer Healthcare LLC (Bayer AG)
• Inventors: First, Eric R., Patel, Ashish B., Schmitz, Guido, Petaway-Hickson, Stephanie, Tong, Hung-Huar
• Application Number:
  US13/373,410
• Publication Number:
  US 20130122098A1
• Time in Patent Office: Days
• US Class Current: 424/490
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 31/5513 1,4-Benzodiazepines, e.g. diazepam or clozapine
• CPC Class Codes: A61K 31/60 Salicylic acid; Derivatives thereof
• CPC Class Codes: A61K 9/143 with inorganic compounds
• CPC Class Codes: A61K 9/2027 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2095 Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing mechanical aspects A61J3/00
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Abstract

A tablet with an enhanced dissolution profile for a medicinally active ingredient such as aspirin and methods for making the tablet. The tablet comprises a blend of crystals of the medicinally active ingredient and a dissolution aid such as sodium or calcium carbonate or bicarbonate that coats the crystals upon co-milling. The blend is then compressed to form tablets that have an enhanced dissolution profile for the medicinally active ingredient.

Claims

1. A blend for forming into a pharmaceutical tablet comprising crystals of a medicinally active ingredient having a particle size less than about 40 μ

m and a dissolution aid, wherein said blend has been sufficiently milled to substantially coat said crystals with said dissolution aid, whereby the dissolution rate of said medicinally active ingredient when formed into a tablet is enhanced compared to the dissolution rate of said active ingredient in a tablet without such milling.

2. The blend of claim 1, wherein said medicinally active ingredient is selected from the group consisting of analgesics, sympathomimetic amine drugs, beta blockers, anti-histamines;

calcium channel blockers, nutritional supplements, Cox-II inhibitors, selective serotonin re-uptake inhibitors, benzodiazepines, codeine and synthetic derivatives, muscle relaxants, and salts and combinations thereof.

3. The blend of claim 1, wherein said medicinally active ingredient is selected from the group consisting of acetaminophen, aspirin, ibuprofen, ketoprofen, naproxen, pseudoephedrine, phenylephrine, and phenylpropanolamine, ranitidine, famotidine, cimetidine and nizatidine;

anti-diphenhydramine hydrochloride, brompheniramine, chlorpheniramine, dimenhydrinate, diphenhydramine, doxylamine, ceterazine hydrochloride, meclizine, loratadine, cartelol, propafenose hydrochloride, pindolol, rimipril, atenolol, bepridil, diltiazem, and verapamil, co-Q10, ginseng, lycopene, glucosamine/chondroitin, S-adenosylmethione, curcumin, holy basil, zinc, omega 3 fatty acids DHA and EPA, Vitamin C, Vitamin E, Saint John'"'"'s Wort, celecoxib, valdecoxib, carisoprodol and aspirin, methocarbamol and aspirin, cyclobenzaprine HCl, clonazepam, diazepam, alprazolam, hydrocodone, oxyocodone and acetaminophen, Hydrocodone Bitartrate and Acetaminophen, Oxycodone Hydrochloride, Acetaminophen and Codeine;

selective serotonin re-uptake inhibitors (SSRIs) salts and combinations thereof.

4. The blend of claim 2, wherein said medicinally active ingredient is selected from the group consisting of acetaminophen, aspirin, ibuprofen, ketoprofen, naproxen and salts and combinations thereof.

5. The blend of claim 1, wherein said dissolution aid is selected from the group consisting of carbonates and bicarbonates.

6. The blend of claim 5, wherein said dissolution aid is selected from the group consisting of sodium, calcium, magnesium and potassium salts of carbonates and bicarbonates.

7. The blend of claim 1, wherein said medicinally active ingredient comprises aspirin and said dissolution aid is selected from the group consisting of sodium and calcium salts of carbonates and bicarbonates.

8. The blend of claim 7, wherein said blend comprises from about 37 mg to about 500 mg aspirin, and said dissolution aid comprises from about 5% to about 40% by weight of aspirin present in said blend.

9. The blend of claim 7, wherein said blend is milled for a period of not less than three minutes, thereby substantially coating said crystals with said dissolution aid.

10. A method for manufacturing a delivery vehicle for a medicinally active ingredient comprising the steps of:

a. Preparing a pre-blend of crystals of said medicinally active ingredient and a dissolution aid;

b. Milling said pre-blend for a time sufficient to establish a particle size of said crystals of not more than about 40 μ

m and to substantially coat said crystals with said dissolution aid to form a blend; and

c. Compressing said blend to form said delivery vehicle.

11. The method of claim 10, further comprising the step of roller compacting said blend before compressing said blend.

12. The method claim 10, wherein said medicinally active ingredient is selected from the group consisting of acetaminophen, aspirin, ibuprofen, ketoprofen, naproxen and salts and combinations thereof.

13. The method of claim 10, wherein said dissolution aid is selected from the group consisting of carbonates and bicarbonates.

14. The method of claim 13, wherein said dissolution aid is selected from the group consisting of sodium and calcium salts of carbonates and bicarbonates.

15. The method of claim 10, wherein said medicinally active ingredient comprises aspirin and said dissolution aid is selected from the group consisting of sodium and calcium salts of carbonates and bicarbonates.

16. The method of claim 15, wherein said blend comprises from about 37 mg to about 500 mg aspirin, and said dissolution aid, comprises from about 5% to about 40% by weight of the amount of aspirin present in said blend.

17. The method of claim 15, wherein said blend is milled for a period of not less than three minutes.