Fexofenadine microcapsules and compositions containing them

• US 9,233,105 B2
• Filed: 10/09/2013
• Issued: 01/12/2016
• Est. Priority Date: 12/02/2009
• Status: Active Grant

• Current Assignee: Adare Pharmaceuticals S.R.L. (Adare Pharmaceuticals, Inc.)
• Original Assignee: Adare Pharmaceuticals S.R.L. (Adare Pharmaceuticals, Inc.)
• Inventors: Mapelli, Luigi, Fabiani, Flavio, Boltri, Luigi, Gatti, Paolo, Serratoni, Mauro, Cassanmagnago, Roberto
• Primary Examiner(s): Arnold, Ernst V
• Application Number:
  US14/049,818
• Publication Number:
  US 20140141091A1
• Time in Patent Office: 825 Days
• US Class Current: 1/1
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 9/5026 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/5042 Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/5047 Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/5089 Processes
• CPC Class Codes: A61P 11/02 Nasal agents, e.g. decongestants
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/04 Antipruritics
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The present invention provides a pharmaceutical composition comprising taste-masked immediate release microcapsules which comprise fexofenadine and a water-insoluble polymer coating. These microcapsules and the pharmaceutical compositions comprising them have suitable drug content and desirable pharmaceutical properties, including a quick dissolution rate of fexofenadine combined with a taste masking effect.

Claims

1. A tasted-masked pharmaceutical composition comprising a water suspendable co-granulate of immediate release microcapsules and at least one inactive ingredient, wherein said microcapsules comprise fexofenadine and a water-insoluble polymer coating.

2. The pharmaceutical composition of claim 1, wherein said fexofenadine is crystalline fexofenadine.

3. The pharmaceutical composition of claim 1, wherein said fexofenadine is fexofenadine hydrochloride.

4. The pharmaceutical composition of claim 1, wherein said water-insoluble polymer is selected from the group consisting of ethylcellulose, polyvinyl acetate, cellulose acetate, cellulose acetate butyrate, polyvinyl acetate, ammonio-methacrylate copolymers and mixtures thereof.

5. The pharmaceutical composition of claim 4, wherein said water-insoluble polymer is ethylcellulose.

6. The pharmaceutical composition of claim 1, wherein the weight of the water insoluble polymer of said microcapsules is from about 2% to about 40%.

7. The pharmaceutical composition of claim 6, the weight of the water insoluble polymer of said microcapsules is from about 10% to about 20%.

8. The pharmaceutical composition of claim 7, wherein the weight of the water insoluble polymer of said microcapsules is from about 13% to about 18%.

9. The pharmaceutical composition of claim 3, wherein said composition releases at least about 60% of said fexofenadine hydrochloride within 15 minutes in pH 6.8 JP 2°

nd fluid.

10. The pharmaceutical composition of claim 9, wherein said composition releases at least about 80% of said fexofenadine hydrochloride within 15 minutes in pH 6.8 JP 2°

nd fluid.

11. The pharmaceutical composition of claim 10, wherein said composition releases at least about 90% of said fexofenadine hydrochloride within 15 minutes in pH 6.8 JP 2°

nd fluid.

12. The pharmaceutical composition of claim 11, wherein said composition releases at least about 95% of said fexofenadine hydrochloride within 15 minutes in pH 6.8 JP 2°

nd fluid.

13. The pharmaceutical composition of claim 1, wherein said microcapsules further comprise a surfactant.

14. The pharmaceutical composition of claim 13, wherein said microcapsules further comprise a glidant or an antisticking agent.

15. The pharmaceutical composition of claim 13, wherein said surfactant is selected from the group consisting of sodium docusate, sorbitan oleate, sorbitan laurate and sodium lauryl sulfate.

16. The pharmaceutical composition of claim 15, wherein said surfactant is sodium docusate.

17. The pharmaceutical composition of claim 1, further comprising additional inactive ingredients which are optionally granulated and/or at least one excipient.

18. The pharmaceutical composition of claim 17, wherein said inactive ingredient is selected from the group consisting of sugar alcohol saccharide, granulated sugar alcohol, and granulated saccharide.

19. The pharmaceutical composition of claim 17, wherein said inactive ingredient is sucrose, xanthan gum, cyclodextrin, and mixtures thereof.

20. The pharmaceutical composition of claim 1, wherein said composition is in the form of a tablet, capsule or sachet.

21. The pharmaceutical composition of claim 1, wherein the co-granule consists of taste masked immediate release microcapsules, xanthan gum and sucrose, wherein the weight ratio of microcapsules to the (xanthan gum+sucrose) is 1:

7.

22. The pharmaceutical composition of claim 17 wherein the ratio of the co-granulated microcapsules to the granulated inactive ingredient is 1:

1.

23. The pharmaceutical composition of claims 21-22 wherein said composition is in the form of sachet.

24. A process for preparing the pharmaceutical composition of claim 1, wherein the pharmaceutical composition comprises taste-masked immediate release microcapsules comprising fexofenadine coated with a water-insoluble polymer, wherein said process comprises the steps of:

(a) dissolving a water-insoluble polymer in an organic solvent;

(b) suspending fexofenadine in said organic solvent;

(c) applying a coating of said water-insoluble polymer onto said fexofenadine by phase separation; and

(d) separating said microcapsules from said organic solvent;

(e) optional wetting of microcapsules;

(f) co-granulating the microcapsules with at least one inactive ingredient;

(g) separately optionally granulating at least one inactive ingredient; and

(h) mixing of co-granulate obtained in step (f) together with the granulated inactive ingredient obtained in step (g).

25. The process of claim 24, wherein said fexofenadine is crystalline fexofenadine.

26. The process of claim 24, wherein said fexofenadine is fexofenadine hydrochloride.

27. The process of claim 26, further comprising the step of drying said separated microcapsules after step (d).

28. The process of claim 27, further comprising the step of adding a phase inducer agent to said organic solvent to promote step (c).

29. The process of claim 28, wherein said phase inducer agent is selected from the group consisting of polyethylene, polyisobutylene, butyl rubber, polybutadiene, organosilicon polymers, and paraffin.

30. The process of claim 29, wherein said phase inducer agent is polyethylene.

31. A process for preparing a taste-masked immediate release pharmaceutical composition in form of sachets comprising the following steps:

(a) dissolving a water-insoluble polymer in an organic solvent;

(b) suspending fexofenadine in said organic solvent;

(c) applying a coating of said water-insoluble polymer onto said fexofenadine by phase separation;

(d) separating said microcapsules from said organic solvent;

(e) optional wetting of microcapsules;

(f) co-granulating the microcapsules with at least one inactive ingredient;

(g) separately granulating at least one inactive ingredient;

Lh) mixing of co-granulate obtained in step (f) together with the granulated inactive ingredient obtained in step (g);

(i) filling the bulk mixture of step (h) in sachets.

32. A method for treating an inflammation related condition in an individual comprising administering to an individual in need thereof a pharmaceutical composition comprising taste-masked immediate release microcapsules or taste masked immediate release co-granulated microcapsules, wherein said microcapsules comprise fexofenadine and a water-insoluble polymer coating.

33. The method of claim 32, wherein said fexofenadine is crystalline fexofenadine.

34. The method of claims 32-33, wherein said fexofenadine is fexofenadine hydrochloride.

35. The method of claim 32, wherein the weight of the water insoluble polymer of said microcapsules is from about 2% to about 40%.

36. The method of claim 34, wherein the weight of the water insoluble polymer of said microcapsules is from about 10% to about 20%.

37. The method of claim 36, wherein the weight of the water insoluble polymer of said microcapsules is from about 13% to about 18%.

38. The method of claim 32, wherein said inflammation related condition is seasonal allergic rhinitis or chronic idiopathic urticaria.

39. The method of claim 38, wherein said inflammation related condition is seasonal allergic rhinitis.

40. The method of claim 38, wherein said inflammation related condition is chronic idiopathic urticaria.

41. The method of claim 32, wherein said water-insoluble polymer is selected from the group consisting of ethylcellulose, polyvinyl acetate, cellulose acetate, cellulose acetate butyrate, polyvinyl acetate, ammonio-methacrylate copolymers and mixtures thereof.

42. The method of claim 41, wherein said water-insoluble polymer is ethylcellulose.

43. The method of claim 32, wherein said composition releases at least about 80% of said fexofenadine hydrochloride within 15 minutes in pH 6.8 JP 2°

nd fluid.

44. The method of claim 43, wherein said composition releases at least about 90% of said fexofenadine hydrochloride within 15 minutes in pH 6.8 JP 2°

nd fluid.

45. The method of claim 32, wherein said microcapsules further comprise a surfactant.

46. The method of claim 44, wherein said microcapsules further comprise a glidant or an antisticking agent.

47. The method of claim 45, wherein said surfactant is selected from the group consisting of sodium docusate, sorbitan oleate, sorbitan laurate and sodium lauryl sulfate.

48. The method of claim 47, wherein said surfactant is sodium docusate.

49. The method of claim 32, wherein said pharmaceutical composition further comprises at least one inactive ingredient which is optionally granulated and/or at least one excipient.

50. The method of claim 49, wherein said inactive ingredient is selected from the group consisting of sugar alcohol, saccharide, granulated sugar alcohol, and granulated saccharide.

51. The method of claim 50, wherein said inactive ingredient is sucrose, xanthan gum, cyclodextrin, and mixtures thereof.

52. The method of claim 32, wherein said pharmaceutical composition is in the form of a tablet, capsule or sachet.

53. The method of claim 52, wherein said pharmaceutical composition is in the form of a sachet.