# US 8,771,729 B2 · Orally administered corticosteroid compositions

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- Number: US 8,771,729 B2
- Document ID: US8771729B2
- Status: Granted
- Kind: B2
- Application number: 12/896,005
- Filed: 2010-10-01
- Published: 2011-04-07
- Granted: 2014-07-08
- Earliest claimed: 2009-10-01
- Assignees: Aptalis Pharmatech, Inc.
- Applicants: Stephen Perrett; Fredric Jay Cohen; Gopi Venkatesh
- Inventors: Stephen Perrett; Fredric Jay Cohen; Gopi Venkatesh
- Web page: https://patentgrep.com/patent/US8771729B2

## CPC

- A61K 9/0065: {Forms with gastric retention, e.g. floating on gastric juice, adhering to gastric mucosa, expanding to prevent passage through the pylorus}
- A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration}
- 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}
- A61K 9/006: {Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays}
- A61K 9/08: Solutions {(composition of solutions A61K47/00)}
- A61K 31/56: Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K 31/569: substituted in position 17 alpha, e.g. ethisterone
- A61K 31/58: containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin (digitoxin {A61K31/7048})
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61K 47/38: Cellulose; Derivatives thereof
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 11/04: for throat disorders
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 31/04: Antibacterial agents
- A61P 31/10: Antimycotics
- A61P 31/12: Antivirals
- A61P 37/02: Immunomodulators
- A61K 9/06: Ointments; Bases therefor; {Other semi-solid forms, e.g. creams, sticks, gels (composition of ointments, creams or gels A61K47/00)}
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention is directed to orally administered corticosteroid compositions. The present invention also provides a method for treating a condition associated with inflammation of the gastrointestinal tract in an individual. The method comprises administering to an individual in need thereof a pharmaceutical composition of the present invention.

## Claims

### Claim 1

An orally disintegrating solid pharmaceutical composition comprising less than or equal to about 20 mg of a topically administrable corticosteroid and at least one disintegrant, wherein the solid pharmaceutical composition has no significant systemic glucocorticoid or mineralocorticoid activity after oral administration,
wherein the solid pharmaceutical composition disintegrates within 60 seconds when tested using the USP <701> Disintegration Test, and
wherein upon administration the corticosteroid is deposited topically in the upper gastrointestinal tract.

### Claim 2 (depends on 1)

The solid pharmaceutical composition of claim 1, wherein said solid pharmaceutical composition disintegrates within 30 seconds.

### Claim 3 (depends on 1)

The solid pharmaceutical composition of claim 1, wherein said corticosteroid is selected from the group consisting of budesonide, fluticasone, flunisolide, ciclesonide, mometasone, beclomethasone, and salts, solvates and esters thereof.

### Claim 4 (depends on 1)

The solid pharmaceutical composition of claim 1, further comprising an adhesive agent.

### Claim 5 (depends on 4)

The solid pharmaceutical composition of claim 4, wherein the adhesive agent is selected from the group consisting of sucrose aluminum sulfate complex, chitosan and derivatives thereof, polyvinylpyrrolidone, methylcellulose, sodium carboxymethylcellulose, hydroxypropyl cellulose, cross-linked or uncross-linked polyacrylates, cross-linked polyacrylates, acidic cross-linked or uncross-linked polyacrylates, polyacrylic acid homopolymers or copolymers, aminoalkyl methacrylate copolymers, methacrylic acid/methylmethacrylate copolymer, alkylacrylate/alkylmethacrylate copolymers, ammoniomethacrylate copolymers, carbomer homopolymers or copolymers, hydrophilic polysaccharide gums, maltodextrins, cross-linked alginate gum gels, polycarboxylated vinyl polymers, pectins, xanthan gums, alginic acid, modified alginic acids, and combinations thereof.

### Claim 6 (depends on 1)

The solid pharmaceutical composition of claim 1, wherein the at least one disintegrant is selected from the group consisting of crospovidone, sodium starch glycolate, crosslinked carboxymethyl cellulose, low-substituted hydroxylpropylcellulose, mannitol, xylitol, sorbitol, maltol, maltitol, lactose, sucrose, maltose, and combinations thereof.

### Claim 7 (depends on 1)

The solid pharmaceutical composition of claim 1, further comprising an excipient selected from the group consisting of mannitol, xylitol, sorbitol, maltol, maltitol, lactose, sucrose, maltose, cyclodextrin, and combinations thereof.

### Claim 8 (depends on 1)

The solid pharmaceutical composition of claim 1, which is substantially free of lubricant.

### Claim 9 (depends on 1)

The solid pharmaceutical composition of claim 1, further comprising at least one antifungal agent.

### Claim 10 (depends on 9)

The solid pharmaceutical composition of claim 9, wherein the antifungal agent is selected from the group consisting of mitotic inhibitor antifungals, pyrimidine analog antifungals, polyene antifungals, benzimidazole antifungals, imidazole antifungals, polyene antifungals, triazole antifungals, thiazole antifungals, allylamine antifungals, echinocandin antifungals, and uncategorized antifungals.

### Claim 11 (depends on 10)

The solid pharmaceutical composition of claim 10, wherein the antifungal agent is selected from the group consisting of anidulafungin, caspofungin, clotrimazole, fluconazole, itraconazole, micafungin, nystatin, posaconazole, and voriconazole.

### Claim 12 (depends on 1)

The solid pharmaceutical composition of claim 1, further comprising at least one antiviral agent.

### Claim 13 (depends on 12)

The solid pharmaceutical composition of claim 12, wherein the antiviral agent is selected from the group consisting of interferons, nucleoside and nucleotide reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, integrase inhibitors, fusion inhibitors, maturation inhibitors, purine analogs, pyrimidine analogs, and uncategorized antiviral drugs.

### Claim 14 (depends on 12)

The solid pharmaceutical composition of claim 12, wherein the antiviral agent selected from the group consisting of aciclovir, brivudine, docosanol, famciclovir, ganciclocvir, idoxuridine, penciclovir, trifluridine, tromantadine, valaciclovir, and valganciclovir.

### Claim 15 (depends on 1)

The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is in the form of an orally disintegrating tablet (ODT).

### Claim 16 (depends on 15)

The pharmaceutical composition of claim 15, wherein the ODT comprises drug particles and rapidly dispersing granules, wherein the drug particles comprise the corticosteroid, and the rapidly dispersing granules comprise the disintegrant and a sugar alcohol and/or saccharide.

### Claim 17 (depends on 16)

The pharmaceutical composition of claim 16, wherein the drug particles have an average particle size of less than about 400 μm, the rapidly dispersing granules have an average particle size of less than about 300 μm, and the disintegrant and sugar alcohol and/or saccharide have an average particle size of less than about 30 μm.

### Claim 18 (depends on 16)

The pharmaceutical composition of claim 16, wherein the drug particles have an average particle size of less than about 4 μm, the rapidly dispersing granules have an average particle size of less than about 300 μm.

### Claim 19 (depends on 16)

The pharmaceutical composition of claim 16, wherein the corticosteroid is disposed over the surface of an excipient, the rapidly dispersing granules have an average particle size of less than about 300 μm.

### Claim 20 (depends on 4)

The pharmaceutical composition of claim 4, wherein the adhesive agent and the corticosteroid are intimately associated.

### Claim 21 (depends on 20)

The pharmaceutical composition of claim 20, wherein said corticosteroid is surrounded or encapsulated by the adhesive agent.

### Claim 22 (depends on 20)

The pharmaceutical composition of claim 20, wherein the corticosteroid is disposed on the surface of said adhesive agent.

### Claim 23 (depends on 16)

The pharmaceutical composition of claim 16, wherein the ODT comprises a lyophilized matrix, wherein the lyophilized matrix comprises the corticosteroid in combination with at least one excipient.

### Claim 24 (depends on 23)

The pharmaceutical composition of claim 23, wherein the excipient is selected from the group consisting of mannitol, xylitol, sorbitol, maltol, maltitol, lactose, sucrose, maltose, and combinations thereof.

### Claim 25 (depends on 23)

The pharmaceutical composition of claim 23, wherein the ODT is in the form of a wafer or film.

### Claim 26 (depends on 16)

The pharmaceutical composition of claim 16, wherein the ODT is in the form of a wafer or film.

### Claim 27

An orally disintegrating tablet comprising less than or equal to about 20 mg of a corticosteroid selected from the group consisting of fluticasone, budesonide, mometasone, and salts, solvates and esters thereof, and at least one disintegrant, wherein the orally disintegrating tablet disintegrates within 60 seconds when tested using the USP <701> Disintegration Test.

### Claim 28 (depends on 27)

The orally disintegrating tablet of claim 27, that comprises from about 2 to about 10 mg fluticasone.

### Claim 29 (depends on 1)

A method for treating an inflammatory condition of the gastrointestinal tract comprising administering to an individual in need thereof a pharmaceutical composition according to claim 1.

### Claim 30 (depends on 29)

The method of claim 29, wherein said inflammation of the gastrointestinal tract comprises inflammation of the esophagus.

### Claim 31 (depends on 29)

The method of claim 29, wherein said condition is eosinophilic esophagitis.

### Claim 32 (depends on 29)

The method of claim 29, wherein said inflammation comprises inflammation of the glottis, epiglottis, tonsils, or oropharynx.

### Claim 33 (depends on 29)

The method of claim 29, wherein said condition is viral or bacterial pharyngitis.

### Claim 34 (depends on 29)

The method of claim 29, wherein said condition is gastroesophageal reflux disease (GERD), nonerosive reflux disease (NERD) or erosive esophagitis.

### Claim 35 (depends on 1)

The solid composition of claim 1, formulated for topical administration to the upper gastrointestinal tract.

### Claim 36 (depends on 35)

The solid composition of claim 35, wherein the upper gastrointestinal tract is further defined as the esophagus.

### Claim 37 (depends on 16)

The pharmaceutical composition of claim 16, wherein the ODT further comprises a sugar alcohol, a disintegrant, and microcrystalline cellulose, wherein the drug particles comprise fluticasone, and the rapidly dispersing granules comprise a disintegrant and a sugar alcohol or saccharide or a mixture thereof.

### Claim 38 (depends on 27)

The orally disintegrating tablet of claim 27, that comprises from about 0.01 mg and about 20 mg fluticasone.

### Claim 39 (depends on 1)

The solid pharmaceutical composition of claim 1, that comprises from about 0.01 mg and about 20 mg fluticasone.

### Claim 40 (depends on 1)

The solid pharmaceutical composition of claim 1, that comprises from about 2 to about 10 mg fluticasone.