Fexofenadine microcapsules and compositions containing them
View Patent ↗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.
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.