FEXOFENADINE MICROCAPSULES AND COMPOSITIONS CONTAINING THEM
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 pharmaceutical composition comprising microcapsules selected from taste-masked immediate release microcapsules or taste-masked immediate release co-granulated microcapsules, and mixtures thereof, wherein said microcapsules comprise fexofenadine and a water-insoluble polymer coating.
2 . The pharmaceutical composition of claim 1 , wherein said microcapsules are taste-masked immediate release co-granulated microcapsules.
3 . The pharmaceutical composition of claims 1 - 2 , wherein said fexofenadine is crystalline fexofenadine.
4 . The pharmaceutical composition of claims 1 - 3 , wherein said fexofenadine is fexofenadine hydrochloride.
5 . The pharmaceutical composition of claims 1 - 4 , 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.
6 . The pharmaceutical composition of claims 5 , wherein said water-insoluble polymer is ethylcellulose.
7 . The pharmaceutical composition of claims 1 - 6 , wherein the weight of the water insoluble polymer of said microcapsules is from about 2% to about 40%.
8 . The pharmaceutical composition of claim 7 , the weight of the water insoluble polymer of said microcapsules is from about 10% to about 20%.
9 . The pharmaceutical composition of claim 8 , wherein the weight of the water insoluble polymer of said microcapsules is from about 13% to about 18%.
10 . The pharmaceutical composition of claim 4 , wherein said composition releases at least about 60% 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 80% 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 90% of said fexofenadine hydrochloride within 15 minutes in pH 6.8 JP 2° nd fluid.
13 . The pharmaceutical composition of claim 12 , wherein said composition releases at least about 95% of said fexofenadine hydrochloride within 15 minutes in pH 6.8 JP 2° nd fluid.
14 . The pharmaceutical composition of claims 1 - 13 , wherein said microcapsules further comprise a surfactant.
15 . The pharmaceutical composition of claim 14 , wherein said microcapsules further comprise a glidant or an antisticking agent.
16 . The pharmaceutical composition of claims 14 - 15 , wherein said surfactant is selected from the group consisting of sodium docusate, sorbitan oleate, sorbitan laurate and sodium lauryl sulfate.
17 . The pharmaceutical composition of claim 16 , wherein said surfactant is sodium docusate.
18 . The pharmaceutical composition of claims 1 - 17 , further comprising at least one inactive ingredient which is optionally granulated and/or at least one excipient.
19 . The pharmaceutical composition of claim 18 , wherein said inactive ingredient is selected from the group consisting of sugar alcohol saccharide, granulated sugar alcohol, and granulated saccharide.
20 . The pharmaceutical composition of claim 18 , wherein said inactive ingredient is sucrose, xanthan gum, cyclodextrin, and mixtures thereof.
21 . The pharmaceutical composition of claims 1 - 20 , wherein said composition is in the form of a tablet, capsule or sachet.
22 . The pharmaceutical composition of claims 1 - 20 , wherein the co-granulated microcapsules 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.
23 . The pharmaceutical composition of claims 17 - 22 wherein the ratio of the co-granulated microcapsules to the granulated inactive ingredient is 1:1.
24 . The pharmaceutical composition of claims 22 - 23 wherein said composition is in the form of sachet.
25 . 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.
26 . The process of claim 25 , wherein said fexofenadine is crystalline fexofenadine.
27 . The process of claim 25 , wherein said fexofenadine is fexofenadine hydrochloride.
28 . The process of claim 27 , further comprising the step (e) drying said separated microcapsules.
29 . The process of claim 28 , further comprising the step of adding a phase inducer agent to said organic solvent to promote step (c).
30 . The process of claim 29 , wherein said phase inducer agent is selected from the group consisting of polyethylene, polyisobutylene, butyl rubber, polybutadiene, organosilicon polymers, and paraffin.
31 . The process of claim 30 , wherein said phase inducer agent is polyethylene.
32 . 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; 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.
33 . 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.
34 . The method of claim 33 , wherein said fexofenadine is crystalline fexofenadine.
35 . The method of claims 33 - 34 , wherein said fexofenadine is fexofenadine hydrochloride.
36 . The method of claim 33 , wherein the weight of the water insoluble polymer of said microcapsules is from about 2% to about 40%.
37 . The method of claim 35 , wherein the weight of the water insoluble polymer of said microcapsules is from about 10% to about 20%.
38 . The method of claim 37 , wherein the weight of the water insoluble polymer of said microcapsules is from about 13% to about 18%.
39 . The method of claim 33 - 38 , wherein said inflammation related condition is seasonal allergic rhinitis or chronic idiopathic urticaria.
40 . The method of claim 39 , wherein said inflammation related condition is seasonal allergic rhinitis.
41 . The method of claim 39 , wherein said inflammation related condition is chronic idiopathic urticaria.
42 . The method of claim 33 - 41 , 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.
43 . The method of claim 42 , wherein said water-insoluble polymer is ethylcellulose.
44 . The method of claims 33 - 43 , wherein said composition releases at least about 80% of said fexofenadine hydrochloride within 15 minutes in pH 6.8 JP 2° nd fluid.
45 . The method of claim 44 , wherein said composition releases at least about 90% of said fexofenadine hydrochloride within 15 minutes in pH 6.8 JP 2° nd fluid.
46 . The method of claims 33 - 43 , wherein said microcapsules further comprise a surfactant.
47 . The method of of claim 45 , wherein said microcapsules further comprise a glidant or an antisticking agent.
48 . The method of claim 46 , wherein said surfactant is selected from the group consisting of sodium docusate, sorbitan oleate, sorbitan laurate and sodium lauryl sulfate.
49 . The method of claim 48 , wherein said surfactant is sodium docusate.
50 . The method of claim 33 - 49 , wherein said pharmaceutical composition further comprises at least one inactive ingredient which is optionally granulated and/or at least one excipient.
51 . The method of claim 50 , wherein said inactive ingredient is selected from the group consisting of sugar alcohol, saccharide, granulated sugar alcohol, and granulated saccharide.
52 . The method of claim 51 , wherein said inactive ingredient is sucrose, xanthan gum, cyclodextrin, and mixtures thereof.
53 . The method of claim 33 - 52 , wherein said pharmaceutical composition is in the form of a tablet, capsule or sachet.
54 . The method of claim 53 , wherein said pharmaceutical composition is in the form of a sachet.