Fexofenadine microcapsules and compositions containing them

• US 8,580,313 B2
• Filed: 12/02/2010
• Issued: 11/12/2013
• Est. Priority Date: 12/02/2009
• Status: Active Grant

• Current Assignee: Adare Pharmaceuticals S.R.L. (Adare Pharmaceuticals, Inc.)
• Original Assignee: Aptalis Pharma Ltd (Abbvie Incorporated)
• Inventors: Mapelli, Luigi, Fabiani, Flavio, Boltri, Luigi, Gatti, Paolo, Serratoni, Mauro, Cassanmagnago, Roberto
• Primary Examiner(s): ARNOLD, ERNST V
• Application Number:
  US12/959,113
• Publication Number:
  US 20110250281A1
• Time in Patent Office: 1,076 Days
• Field of Search: None
• US Class Current: 424/495
• 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 pharmaceutical composition comprising a water suspendable co-granulate of taste-masked immediate release microcapsules, wherein said microcapsules comprise fexofenadine coated with 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, 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 3, wherein said composition releases at least about 60% of said fexofenadine hydrochloride within 15 minutes in pH 6.8 JP 2°

nd fluid.

8. The pharmaceutical composition of claim 1, wherein said microcapsules further comprise a surfactant, a glidant and/or an antisticking agent.

9. The pharmaceutical composition of claim 1, further comprising at least one inactive ingredient which is optionally granulated and/or at least one excipient.

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

11. The pharmaceutical composition of claim 1, further comprising sodium docusate, and one or more granulated inactive ingredients;

wherein the weight ratio of the co-granulated microcapsules to the granulated inactive ingredients is 1;

1.

12. The pharmaceutical composition of claim 1, wherein the co-granulated microcapsules consist of taste-masked immediate release microcapsules, xanthan gum, and sucrose powder granulated together, wherein the weight ratio of the taste-masked immediate release microcapsules to sucrose powder is between 1:

6 and 1;

7.

13. The pharmaceutical composition of claim 12, wherein the co-granulated microcapsules consist of taste masked immediate release microcapsules, xanthan gum and sucrose, wherein the weight ratio of microcapsules to sucrose powder is about 1:

7.

14. The pharmaceutical composition of claim 13, wherein the co-granulated microcapsules have a fine fraction below 125 μ

m of <

5.0%, and a fraction over 600 μ

m which is <

10.0%.

15. The pharmaceutical composition of claim 13, wherein the co-granulated microcapsules have a fine fraction below 125 μ

m of <

5.0%, and a fraction over 600 μ

m of <

5.0%.

16. 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.

17. The process of claim 16, wherein said fexofenadine is crystalline fexofenadine.

18. The process of claim 16, wherein said fexofenadine is fexofenadine hydrochloride.

19. The process of claim 18, further comprising the step of adding a phase inducer agent to said organic solvent to promote step (c).

20. The process of claim 19, wherein said phase inducer agent is selected from the group consisting of polyethylene, polyisobutylene, butyl rubber, polybutadiene, organosilicon polymers, and paraffin.

21. The process of claim 18, further comprising the following steps:

(e) optional wetting of microcapsules;

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

(g) separately granulating at least one inactive ingredient;

h) 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.

22. The process of claim 21, wherein the inactive ingredient of step f) is sucrose, and wherein the step f) is carried out in the presence of an aqueous binder solution comprising sucrose and xanthan gum.

23. The process of claim 22, wherein the weight ratio of sucrose to xanthan gum in the aqueous binder solution is between 5:

0 to 15;

0.5.

24. 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.

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

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

27. The method of claim 24, wherein the weight of the water insoluble polymer of said microcapsules is from about 2% to about 40%.

28. The method of claim 24, wherein said inflammation related condition is seasonal allergic rhinitis or chronic idiopathic urticaria.

29. The method of claim 24, wherein said water-insoluble polymer is selected from the group consisting of ethylcellulose, polyvinyl acetate, cellulose acetate, cellulose acetate butyrate, ammonio-methacrylate copolymers and mixtures thereof.

30. The method of claim 24, wherein said composition releases at least about 80% of said fexofenadine hydrochloride within 15 minutes in pH 6.8 JP 2°

nd fluid.

31. The method of claims 24-27, 28 or 29 wherein said microcapsules further comprise a surfactant, a glidant and/or an antisticking agent.

32. The method of claim 24 wherein said pharmaceutical composition further comprises at least one inactive ingredient which is optionally granulated and/or at least one excipient.

33. The method of claim 24, wherein said pharmaceutical composition is in the form of a tablet, capsule or sachet.