Mucoadhesive pharmaceutical compositions of corticosteroids

Patent metadata

Field	Value
Publication number	US-2021379081-A1
Application number	US-201917288385-A
Country	US
Kind code	A1
Filing date	Oct 23, 2019
Priority date	Oct 24, 2018
Publication date	Dec 9, 2021
Grant date	—

Abstract

Described herein are mucoadhesive pharmaceutical compositions of corticosteroids, as well as methods of making such pharmaceutical compositions, and therapeutic methods using them. The compositions typically comprise a corticosteroid in a mucoadhesive system, wherein the mucoadhesive system comprises a rheology-modifying agent and a vehicle for the corticosteroid. The compositions are particularly useful for treating inflammatory conditions of the esophagus, such as eosinophilic esophagitis, or inflammatory bowel disease.

First claim

What is claimed is:

1 . A mucoadhesive pharmaceutical corticosteroid composition comprising:
a corticosteroid in a mucoadhesive system, wherein the mucoadhesive system comprises a vehicle for the corticosteroid, a rheology-modifying agent, and optionally, an aqueous acidic buffer, wherein: the composition exhibits a Work of Adhesion of 150 to 350 g/s when assessed by the in vitro texture analysis described herein in Example 2, and/or the composition adheres to esophageal or rectal mucosal tissue for at least 0.5 minutes after administration

2 . The composition of claim 1 , wherein the corticosteroid is one or more selected from budesonide, fluticasone, and ciclesonide.

3 . The composition of claim 1 , wherein the corticosteroid is budesonide.

4 . The composition of claim 1 , wherein the corticosteroid is fluticasone.

5 . The composition of claim 1 , wherein the corticosteroid is ciclesonide.

6 . The composition of any one of claims 1 - 5 , wherein the corticosteroid is present in an amount of 0.01 to 1% w/w of the composition.

7 . The composition of claim 1 , wherein the corticosteroid is budesonide and is present in an amount of about 0.025% w/w of the composition.

8 . The composition of claim 1 , wherein the corticosteroid is budesonide and is present in an amount of about 0.05% w/w of the composition.

9 . The composition of any one of claims 1 - 8 , wherein the vehicle is or comprises glycerin.

10 . The composition of any one of claim 9 , wherein the glycerin is present in an amount of 40 to 70% w/w of the composition.

11 . The composition of any one of claim 9 , wherein the glycerin is present in an amount of about 50% w/w of the composition.

12 . The composition of any one of claims 9 - 11 , wherein the vehicle further comprises propylene glycol.

13 . The composition of claim 12 , wherein the propylene glycol is present in an amount of from 0.5 to 20% w/w of the composition.

14 . The composition of claim 12 , wherein the propylene glycol is present in an amount of about 20% w/w of the composition.

15 . The composition of any one of claims 1 - 14 , wherein the rheology-modifying agent is or comprises xanthan gum.

16 . The composition of claim 15 , wherein the xanthan gum is present in an amount of 0.25 to 1.5% w/w of the composition.

17 . The composition of claim 15 , wherein the xanthan gum is present in an amount of 1% w/w of the composition.

18 . The composition of any one of claims 1 - 17 , wherein the aqueous acidic buffer is selected from a citric acid buffer and an acetate buffer at pH of 4.5 to 5.5.

19 . The composition of claim 18 , wherein the aqueous acidic buffer is a citric acid buffer at pH 5.0±0.1.

20 . The composition of any one of claims 1 - 19 , further comprising one or more pharmaceutically acceptable excipients.

21 . The composition of any one of claims 1 - 20 , further comprising a sweetener.

22 . The composition of claim 21 , wherein the sweetener is or comprises sucralose.

23 . The composition of claim 22 , wherein sucralose is present in an amount from 0.001% to 0.5% of the composition.

24 . The composition of claim 22 , wherein sucralose is present in an amount from 0.01% to 0.05 w/w of the composition.

25 . The composition of claim 22 , wherein sucralose is present in an amount of about 0.005%, 0.01%, 0.05%, or 0.1% w/w of the composition.

26 . The composition of any one of claims 1 - 25 , wherein the composition exhibits substantially similar viscosity and/or mucoadhesive properties over a temperature ranging from 20−40° C.

27 . The composition of any one of claims 1 - 26 , wherein the composition is flowable at room temperature.

28 . The composition of any one of claims 1 - 27 , wherein the composition has a viscosity of about 3000-9000 cps at room temperature.

29 . A mucoadhesive pharmaceutical corticosteroid composition comprising:
(a) budesonide in an amount from 0.02 to 0.06% w/w of the composition, (b) glycerin in an amount from 40 to 70% w/w of the composition, (c) xanthan gum in an amount from 0.25 to 1.5 w/w of the composition, and (d) an aqueous citric acid buffer at pH 5.0±0.1.

30 . The composition of claim 29 , further comprising sucralose in an amount from 0.05 to 0.5% w/w of the composition.

31 . The composition of any one of claims 29 - 30 , further comprising propylene glycol in an amount up to 20% w/w of the composition.

32 . The composition of any one of claims 29 - 31 , comprising:
(a) budesonide in an amount of about 0.05% w/w of the composition, (b) glycerin in an amount of about 50% w/w of the composition, and (c) xanthan gum in an amount of about 1% w/w of the composition.

33 . The composition of claim 32 , comprising sucralose in an amount of about 0.05% w/w of the composition.

34 . The composition of any one of claims 1 - 33 , further comprising a flavoring agent.

35 . The composition of any one of claims 1 - 34 , wherein the composition is a suspension.

36 . The composition of any one of claims 1 - 34 , wherein the composition is a solution.

37 . The composition of any one of claims 1 - 36 , further comprising a preservative.

38 . The composition of claim 37 , wherein the preservative is present in an amount from about 0.01% to about 1.0% w/w of the composition.

39 . The composition of any one of claims 1 - 38 , further comprising an antioxidant.

40 . The composition of claim 39 , wherein the antioxidant is present in an amount from about 0.01% to about 1.0% w/w of the composition.

41 . The composition of any one of claims 37 - 40 , wherein the preservative or antioxidant is or comprises one or more selected from ascorbic acid, EDTA, sodium edetate, and a sulfite.

42 . The composition of any one of claims 1 - 36 , wherein the composition is substantially free of preservatives.

43 . The composition of any one of the preceding claims, wherein the composition exhibits a work of adhesion of 150 to 350 g/s.

44 . The composition of any one of claims 1 - 43 , formulated for oral administration.

45 . The composition of claim 44 , provided in a unit dose package containing from 1 to 10 mL of the composition.

46 . The composition of claim 44 , provided in a unit dose package containing from 2 to 5 mL of the composition.

47 . The composition of any one of claims 1 - 43 , formulated for rectal administration.

48 . The composition of any one of claims 44 - 46 , for use in treating an inflammatory condition of the esophagus.

49 . The composition of any one of claims 44 - 46 , for use in treating eosinophilic esophagitis.

50 . The composition of any one of claims 44 - 47 , for use in treating an inflammatory bowel disease.

51 . A method of treating an inflammatory condition of the esophagus, comprising orally administering a composition according to any one of claims 44 - 46 to a subject in need thereof.

52 . A method o

Assignees

• Ferring Bv

Inventors

• Grenier Arnaud
• Carrara Dario

Classifications

• A61P1/00

  Drugs for disorders of the alimentary tract or the digestive system · CPC title

• A61K31/58

  containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin (digitoxin {A61K31/7048}) · CPC title

• A61K31/56 Primary

  Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids · CPC title

• A61K9/0031 Primary

  Rectum, anus · CPC title

• A61K47/36

  Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin · CPC title