COMBINATION TABLET WITH CHEWABLE OUTER LAYER

• US 20100166810A1
• Filed: 12/23/2009
• Published: 07/01/2010
• Est. Priority Date: 07/01/2007
• Status: Active Grant

• Current Assignee: Vitalis LLC
• Original Assignee: Vitalis LLC
• Inventors: Habboushe, Joseph Peter
• Granted Patent: US 8,404,275 B2
• Time in Patent Office: Days
• US Class Current: 424/400
• CPC Class Codes: A61K 31/455 Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
• CPC Class Codes: A61K 31/616 by carboxylic acids, e.g. acetylsalicylic acid
• CPC Class Codes: A61K 9/0056 Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
• CPC Class Codes: A61K 9/20 Pills, tablets, discs, rods A61K9/0004, A61K9/0007, A61K9/0056, A61K9/0065 take precedence; for reconstitution of a drink A61K9/0095
• CPC Class Codes: A61K 9/209 containing drug in at least two layers or in the core and in at least one outer layer
• CPC Class Codes: A61K 9/28 Dragees; Coated pills or tablets , e.g. with film or compression coating A61K9/2072 takes precedence, e.g. partially coated tablets A61K9/2072, coated multilayer tablets A61K9/2086, tablets with drug-coated core A61K9/209
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid

Abstract

A pharmaceutical composition in the form of a combination tablet is described. The tablet has a rapidly absorbed component that enters the circulation by traversing the buccal mucosa, oral mucosa and combinations thereof, and a more slowly absorbed component that is swallowed. The therapeutic agent in the swallowed portion is absorbed across the gastric mucosa. The combination tablet may be modified, by varying the specific combinations of excipients, fillers, and the like to effect distinct release rates. In addition, the rapid and slow components may have identical or different therapeutic agents depending on the application to a specific medical condition. One embodiment of the combination tablet includes a prostaglandin inhibitor in the rapidly absorbed component in order to mitigate the side effects of immediate release niacin that is in the slow absorbing component. Such combination compositions will increase patient compliance with various dosing regimens due to the resultant decrease in the number of tablets that a patient would need to take on a daily basis.

Claims

1. A pharmaceutical composition comprising;

(a) an inner component comprising an effective amount of a first therapeutic agent, wherein the ingestible component releases the first therapeutic agent by dissolving in stomach, intestines, or further distal in the gastrointestinal tract; and

(b) two or more discrete pulverizable outer layers, each of the discrete pulverizable outer layers comprising at least one second therapeutic agent, the two or more discrete pulverizable outer layers comprising an effective amount of two or more second therapeutic agents, wherein the two or more discrete pulverizable layers are dispersed in the oral cavity by masticating, sucking, dissolving, releasing, or other common means, thereby releasing the two or more second therapeutic agents into the oral cavity where they enter the circulatory system by traversing the buccal mucosa, oral mucosa or combinations thereof;

wherein (a) and (b) further comprise one or more pharmaceutically acceptable excipients, carriers or diluents.

2. The pharmaceutical composition of claim 1,

wherein the inner component is a delayed or extended release dosage form that is at least partially surrounded by the two or more discrete pulverizable outer layers.

3. The pharmaceutical composition of claim 1, wherein the first therapeutic agent is niacin, immediate-release niacin or extended release niacin, and combinations thereof.

4. The pharmaceutical composition of claim 1, wherein at least one of the two or more second therapeutic agents is selected from anti-flushing agents which include but are not limited to the group consisting of an inhibitor of cyclooxygenase I, an inhibitor of cyclooxygenase II, aspirin, diclofenac and laropiprant.

5. The pharmaceutical composition of claim 1, wherein the inner component comprises an effective amount of niacin and optionally, an effective amount of an anti-flush agent such as an NSAID or a COX inhibitor, and wherein at least one of the two or more discrete pulverizable outer layers is selected from the group consisting of anti-flush agents such as an NSAID and a COX inhibitor.

6. The pharmaceutical composition of claim 1, wherein at least one of the two or more discrete pulverizable outer layers comprise at least one pharmaceutically acceptable excipient, carrier or diluent, selected from the group consisting of glucose, maltose, sucrose, dextrose, fructose, sorbitol, mannitol, natural and artificial sweeteners, xanthan gum, methylcelluloses such as sodium carboxymethylcellulose or hydroxypropylmethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, alginates, tragacanth, soluble starch sugars polyalcohols, microcrystalline cellulose, magnesium stearate, carboxymethyl cellulose or low-substituted hydroxypropyl cellulose (L-HPC), polyvinylpyrrolidone XL and carboxymethylamide and combinations thereof or a hydrophilic layer comprising at least one pharmaceutically acceptable excipient, carrier or diluent, selected from the group consisting of sugar, sugar alcohol, polyethylene glycol (PEG), or polyethylene oxide, sorbitol, mannitol, maltitol, reduced starch saccharide, xylitol, reduced paratinose, erythritol, glucose, gelatin, partially hydrolyzed gelatin, hydrolyzed dextran, dextrin, alginate and combinations thereof.

7. The pharmaceutical composition of claim 1, wherein (a) comprises an enteric coating selected from the group consisting of copolymecellulose acetate phthalate, alginates, alkali-soluble acrylic resins, hydroxypropyl methylcellulose phthalate, methacrylate-methacrylic acid copolymers, polyvinyl acetate phthalate and styrol maleic acid copolymers.

8. The pharmaceutical composition of claim 2, wherein the inner component is surrounded on one hemisphere by the two or more discrete pulverizable outer layers.

9. The pharmaceutical composition of claim 1, wherein the inner component comprises an effective amount of niacin and optionally, an effective amount of either an anti-flush agent comprising an NSAID, a COX inhibitor, laropiprant or combinations thereof, and wherein the two or more discrete pulverizable outer layers comprise aspirin and diclofenac in one or more of the two or more discrete pulverizable outer layers.

10. The pharmaceutical composition of claim 9, wherein the inner component comprises an effective amount of niacin and optionally, an effective amount of either an anti-flush agent comprising an NSAID, a COX inhibitor, laropiprant or combinations thereof, and wherein the two or more discrete pulverizable outer layers comprises aspirin and ibuprofen in one or more of the two or more discrete pulverizable outer layers.

11. A pharmaceutical composition comprising;

(a) a swallowable portion comprising an effective amount of a first therapeutic agent, wherein the ingestible component releases the first therapeutic agent by dissolving in the stomach, intestines, or further distal in the gastrointestinal tract; and

(b) an absorbed-in-mouth portion comprising an effective amount of two or more second therapeutic agents, wherein the absorbed-in-mouth portion is dispersed in the oral cavity by masticating, sucking, dissolving, releasing, or other common means, thereby releasing the two or more second therapeutic agents into the oral cavity where they enter the circulatory system by traversing the oral mucosa buccal mucosa and combinations thereof;

wherein (a) and (b) further comprise one or more pharmaceutically acceptable excipients, carriers or diluents.

12. The pharmaceutical composition of claim 11,

wherein the swallowable portion is a delayed or extended release dosage form that is at least partially surrounded by the absorbed-in-mouth portion.

13. The pharmaceutical composition of claim 11, wherein the first therapeutic agent is niacin, immediate-release niacin or extended release niacin, and combinations thereof.

14. The pharmaceutical composition of claim 11, wherein at least one of the two or more second therapeutic agents is selected from anti-flushing agents which include but are not limited to the group agents consisting of an inhibitor of cylcooxygenase I, an inhibitor of cyclooxygenase II, aspirin, diclofenac and laropiprant.

15. The pharmaceutical composition of claim 11, wherein the swallowable portion comprises an effective amount of niacin and optionally, an effective amount of either NSAID or a COX inhibitor or laropiprant, and wherein the absorbed-in-mouth portion comprises at least one anti-flush agent comprising an NSAID, a COX inhibitor, laropiprant and combinations thereof.

16. The pharmaceutical composition of claim 11, wherein the swallowable portion comprises an effective amount of niacin and optionally, an effective amount of either an anti-flush agent comprising an NSAID, a COX inhibitor, laropiprant or combinations thereof, and wherein the absorbed-in-mouth portion comprises aspirin and diclofenac.

17. The pharmaceutical composition of claim 11, wherein the swallowable portion comprises an effective amount of niacin and optionally, an effective amount of either an anti-flush agent comprising an NSAID, a COX inhibitor, laropiprant or combinations thereof, and wherein the absorbed-in-mouth portion comprises aspirin and ibuprofen.

18. The pharmaceutical composition of claim 11, wherein at least one of the two or more second therapeutic agents comprise at least one pharmaceutically acceptable excipient, carrier or diluent, selected from the group consisting of glucose, maltose, sucrose, dextrose, fructose, sorbitol, mannitol, natural and artificial sweeteners, xanthan gum, methylcelluloses such as sodium carboxymethylcellulose or hydroxypropylmethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, alginates, tragacanth, soluble starch sugars polyalcohols, microcrystalline cellulose, magnesium stearate, carboxymethyl cellulose or low-substituted hydroxypropyl cellulose (L-HPC), polyvinylpyrrolidone XL and carboxymethylamide and combinations thereof or a hydrophilic layer comprising at least one pharmaceutically acceptable excipient, carrier or diluent, selected from the group consisting of sugar, sugar alcohol, polyethylene glycol (PEG), or polyethylene oxide, sorbitol, mannitol, maltitol, reduced starch saccharide, xylitol, reduced paratinose, erythritol, glucose, gelatin, partially hydrolyzed gelatin, hydrolyzed dextran, dextrin, alginate and combinations thereof.

19. The pharmaceutical composition of claim 11, wherein (a) comprises an enteric coating selected from the group consisting of copolymecellulose acetate phthalate, alginates, alkali-soluble acrylic resins, hydroxypropyl methylcellulose phthalate, methacrylate-methacrylic acid copolymers, polyvinyl acetate phthalate and styrol maleic acid copolymers.

20. The pharmaceutical composition of claim 12,

wherein the swallowable portion is surrounded on one hemisphere by the absorbed-in-mouth portion.

21. A method of reducing the serum levels in a subject in need thereof, of one or more of the following, triglycerides, total cholesterol, low density lipoprotein cholesterol, and lipoprotein (a), by administering to said subject an effective amount of the composition of claim 18.

22. A method of preventing elevated serum levels in a subject in need thereof, of one or more of the following, triglycerides, total cholesterol, low density lipoprotein cholesterol, lipoprotein (a), by administering to said subject an effective amount of the composition of claim 18.

23. A method of increasing HDL cholesterol in a subject in need thereof, by administering to said subject an effective amount of the composition of claim 18.