Bepotastine compositions

Abstract

Novel compositions including bepotastine besilate and a corticosteroid are provided, compositions including at least about 0.008% w/v benzalkonium chloride, and compositions including hydroxypropylmethyl cellulose E15 LV.

1 - 68 . (canceled) 
     
     
         69 . A pharmaceutical composition comprising at least one corticosteroid as a free form, pharmaceutically acceptable salt, solvate, or physiologically functional derivative thereof, and bepotastine as a free base, pharmaceutically acceptable salt, solvate or physiologically functional derivative thereof, the bepotastine at a concentration from 0.5% w/v to 8.00% w/v inclusive, with at least one pharmaceutically compatible excipient, the composition formulated as a nasal spray. 
     
     
         70 . The composition of  claim 69  wherein the bepotastine concentration is from 2.00% w/v to 4.00% w/v inclusive. 
     
     
         71 . The composition of  claim 69  wherein the excipient is a viscosity enhancing agent and is hydroxypropylmethyl cellulose (HPMC). 
     
     
         72 . The composition of  claim 69  further comprising a preservative. 
     
     
         73 . The composition of  claim 72  wherein the preservative is benzalkonium chloride. 
     
     
         74 . The composition of  claim 69  further comprising at least one pharmaceutically compatible buffer, a tonicity agent, a chelating agent, and an optional taste-masking agent. 
     
     
         75 . The composition of  claim 74  wherein the pharmaceutically compatible buffer is each of a phosphate buffer and a citrate buffer. 
     
     
         76 . The composition of  claim 74  wherein the tonicity agent is sodium chloride. 
     
     
         77 . The composition of  claim 74  wherein the chelating agent is ethylenediamine tetraacetic acid. 
     
     
         78 . The composition of  claim 69  wherein the excipient is a suspending agent comprising a blend of microcrystalline cellulose and carboxymethyl cellulose (AVICEL®) and/or polyoxyethylene (20) sorbitan monooleate (polysorbate 80). 
     
     
         79 . The composition of  claim 69  wherein the excipient is a suspending agent comprising HPMC, AVICEL®, and polysorbate 80. 
     
     
         80 . The composition of  claim 78  or  claim 79  wherein the concentration of the suspending agent is 0.5% w/v-2.5% w/v for AVICEL® and is 0.005% w/v-0.050% w/v for polysorbate 80. 
     
     
         81 . The composition of  claim 74  wherein the optional taste-making agent is (tri)sodium citrate, sodium citrate, sodium chloride, sodium bicarbonate, a polyol sweetener, a high intensity sweetener, and/or a flavoring agent. 
     
     
         82 . The composition of  claim 74  wherein the optional taste-masking agent is sucralose. 
     
     
         83 . The composition of  claim 69  where the pharmaceutically acceptable bepotastine salt is besilate. 
     
     
         84 . The composition of  claim 69  wherein the corticosteroid concentration is from 0.01% w/v to 1% w/v inclusive, and the corticosteroid is selected from the group consisting of beclomethasone, beclomethasone dipropionate, mometasone furoate monohydrate, fluticasone propionate, fluticasone furoate, triamcinolone, triamcinolone acetonide, budesonide, budesonide free acid, ciclesonide, beclomethasone sodium, dexamethasone sodium, prednisolone acetate, and mixtures thereof. 
     
     
         85 . A pharmaceutical composition comprising bepotastine besilate and a corticosteroid free form, pharmaceutically acceptable salt, solvate, or physiologically functional derivative thereof, dibasic sodium phosphate heptahydrate, sodium chloride, edetate disodium, benzalkonium chloride, and one of either:
 a blend of microcrystalline cellulose and carboxymethyl cellulose (AVICEL®) and/or polyoxyethylene (20) sorbitan monooleate (polysorbate 80), or   hydroxypropylmethyl cellulose (HPMC), citric acid monohydrate, and a taste making agent.   
     
     
         86 . The composition of  claim 85  wherein
 the concentration of bepotastine besilate is 0.5% w/v to 8.00% w/v; 
 the concentration of corticosteroid is 0.01% w/v to 1.00% w/v; 
 the concentration of dibasic sodium phosphate heptahydrate is 0.10% w/v to 1.00% w/v; 
 the concentration of sodium chloride is 0.9% w/v with 0.5% bepotastine, 0.4% w/v with 2.00%-3.00% bepotastine, 0.3% w/v with 4.00% bepotastine, 0.2% w/v with 6.00% bepotastine, 0.1% w/v with 8.00% bepotastine; 
 the concentration of edetate disodium is 0.005% w/v to 0.100% w/v; 
 the concentration of benzalkonium chloride is 0.002% w/v to 0.200% w/v; and 
 if used, AVICEL® is AVICEL® CL-611 at a concentration of 0.5% w/v to 2.5% w/v, and the concentration of polysorbate 80 is 0.005% w/v to 0.050% w/v; or 
 if used, the concentration of HPMC is 0.01% w/v to 1.00% w/v, the concentration of citric acid monohydrate is 0.10% w/v to 1.00% w/v, and the concentration of the taste-making agent is 0.01% w/v to 1.00% w/v. 
 
     
     
         87 . The composition of  claim 85  wherein the concentration of bepotastine besilate is 4.00% w/v, the concentration of corticosteroid is 0.05% w/v, the concentration of dibasic sodium phosphate heptahydrate is 0.70% w/v, the concentration of sodium chloride is 0.30% w/v, the concentration of edetate disodium is 0.020% w/v, the concentration of benzalkonium chloride is 0.020% w/v, and
 if used, AVICEL® is AVICEL® CL-611 at a concentration of 2.00% w/v and the concentration of polysorbate 80 is 0.015% w/v; or 
 if used, HPMC is HPMC E15 LV at a concentration of 0.10% w/v, the concentration of citric acid monohydrate is 0.10% w/v, and the taste-masking agent is sucralose and the concentration thereof is 0.10% w/v. 
 
     
     
         88 . A kit comprising a metered dose plunger spray pump coupled with a container containing the composition of  claim 69 , and instructions for administering the composition using the metered dose plunger spray pump. 
     
     
         89 . A pharmaceutical composition comprising a pharmaceutically acceptable salt of bepotastine and at least one corticosteroid, dibasic sodium phosphate heptahydrate, sodium chloride, edetate disodium, benzalkonium chloride, a blend of microcrystalline cellulose and carboxymethyl cellulose (AVICEL®), and/or polyoxyethylene (20) sorbitan monooleate (polysorbate 80). 
     
     
         90 . A pharmaceutical composition comprising a pharmaceutically acceptable salt of bepotastine and at least one corticosteroid, dibasic sodium phosphate heptahydrate, sodium chloride, edetate disodium, benzalkonium chloride, hydroxypropylmethyl cellulose (HPMC), citric acid monohydrate, and a taste making agent. 
     
     
         91 . The composition of  claim 89  wherein
 the pharmaceutically acceptable salt of bepotastine is besilate and the concentration of bepotastine is 0.5% w/v to 8.00% w/v; 
 the concentration of corticosteroid is 0.01% w/v to 1% w/v; 
 the concentration of dibasic sodium phosphate heptahydrate is 0.10% w/v to 1.00% w/v; 
 the concentration of sodium chloride is 0.9% w/v with 0.5% bepotastine, 0.4% w/v with 2.00%-3.00% bepotastine, 0.3% w/v with 4.00% bepotastine, 0.2% w/v with 6.00% bepotastine, 0.1% w/v with 8.00% bepotastine; 
 the concentration of edetate disodium is 0.005% w/v to 0.100% w/v; 
 the concentration of benzalkonium chloride is 0.002% w/v to 0.200% w/v; 
 the concentration of AVICEL® is 0.5% w/v to 2.5% w/v; and the concentration of polysorbate 80 is 0.005% w/v to 0.050% w/v. 
 
     
     
         92 . The composition of  claim 90  wherein
 the pharmaceutically acceptable salt of bepotastine is besilate and the concentration of bepotastine is 0.5% w/v to 8.00% w/v; 
 the concentration of corticosteroid is 0.01% w/v to 1% w/v; 
 the concentration of dibasic sodium phosphate heptahydrate is 0.10% w/v to 1.00% w/v; 
 the concentration of sodium chloride is 0.9% w/v with 0.5% bepotastine, 0.4% w/v with 2.00%-3.00% bepotastine, 0.3% w/v with 4.00% bepotastine, 0.2% w/v with 6.00% bepotastine, 0.1% w/v with 8.00% bepotastine; 
 the concentration of edetate disodium is 0.005% w/v to 0.100% w/v; 
 the concentration of benzalkonium chloride is 0.002% w/v to 0.200% w/v; 
 HPMC is HPMC E15 LV at a concentration of 0.01% w/v to 1.00% w/v, the concentration of citric acid monohydrate is 0.10% w/v to 1.00% w/v, and the concentration of the taste-making agent is 0.01% w/v to 1.00% w/v. 
 
     
     
         93 . The composition of  claim 89  wherein the concentration of bepotastine besilate is 4.00% w/v, the concentration of corticosteroid is 0.01% w/v to 1% w/v, the concentration of dibasic sodium phosphate heptahydrate is 0.70% w/v, the concentration of sodium chloride is 0.30% w/v, the concentration of edetate disodium is 0.020% w/v, the concentration of benzalkonium chloride is 0.020% w/v, AVICEL® is AVICEL® CL-611 at a concentration of 2.00% w/v, and the concentration of polysorbate 80 is 0.015% w/v. 
     
     
         94 . The composition of  claim 90  wherein the concentration of bepotastine besilate is 4.00% w/v, the concentration of corticosteroid is 0.01% w/v to 1% w/v, the concentration of dibasic sodium phosphate heptahydrate is 0.70% w/v, the concentration of sodium chloride is 0.30% w/v, the concentration of edetate disodium is 0.020% w/v, the concentration of benzalkonium chloride is 0.020% w/v, HPMC is HPMC E15 LV at a concentration of 0.10% w/v, the concentration of citric acid monohydrate is 0.10% w/v, and the taste-masking agent is sucralose and the concentration thereof is 0.10% w/v. 
     
     
         95 . A pharmaceutical composition comprising at least one corticosteroid as a free form, pharmaceutically acceptable salt, solvate, or physiologically functional derivative thereof, and bepotastine as a free base, pharmaceutically acceptable salt, solvate or physiologically functional derivative thereof, the bepotastine at a concentration from 0.5% w/v to 8.00% w/v inclusive, and a suspending agent interchangeable with a viscosity enhancing agent, the composition formulated as a nasal spray. 
     
     
         96 . The kit of  claim 88  wherein the composition is formulated as a nasal spray, nasal drops, nasal droplets, or combinations thereof.