Fexofenadine microcapsules and compositions containing them

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.

What is claimed is: 
     
         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  claim 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 2ºnd 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 2ºnd 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 2ºnd 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 2ºnd 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 2ºnd 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 2ºnd fluid. 
     
     
         46 . The method of  claims 33 - 43 , wherein said microcapsules further comprise a surfactant. 
     
     
         47 . The method 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.