BEPOTASTINE COMPOSITIONS
Novel compositions including bepotastine besilate are provided such as sorbitol-free compositions, compositions including at least about 0.008% w/v benzalkonium chloride, and compositions including hydroxypropylmethyl cellulose E15 LV.
1 - 58 . (canceled)
59 . A pharmaceutical composition comprising a pharmaceutically acceptable salt of bepotastine at a concentration from 0.5% w/v to 8.00% w/v inclusive with at least one pharmaceutically compatible excipient, the composition being sorbitol-free or substantially free of sorbitol and formulated as a nasal spray.
60 . The composition of claim 59 wherein the bepotastine concentration is from 2.00% w/v to 4.00% w/v inclusive.
61 . The composition of claim 59 further comprising hydroxypropylmethyl cellulose (HPMC).
62 . The composition of claim 59 further comprising benzalkonium chloride.
63 . The composition of claim 59 further comprising at least one pharmaceutically compatible buffer, a tonicity agent, a chelating agent, an optional suspending agent, and an optional taste-masking agent.
64 . The composition of claim 63 wherein the pharmaceutically compatible buffer is each of a phosphate buffer and a citrate buffer.
65 . The composition of claim 63 wherein the tonicity agent is sodium chloride.
66 . The composition of claim 63 wherein the chelating agent is ethylenediamine tetraacetic acid.
67 . The composition of claim 63 wherein the optional suspending agent is a blend of microcrystalline cellulose and carboxymethyl cellulose (AVICEL®) and/or polyoxyethylene (20) sorbitan monooleate (polysorbate 80).
68 . The composition of claim 63 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.
69 . The composition of claim 63 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.
70 . The composition of claim 63 wherein the optional taste-masking agent is sucralose.
71 . The composition of claim 59 where the pharmaceutically acceptable bepotastine salt is besilate.
72 . A pharmaceutical composition comprising bepotastine besilate, 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.
73 . The composition of claim 72 wherein
the concentration of bepotastine besilate is 0.5% w/v to 8.00% 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 from 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.
74 . The composition of claim 72 wherein the concentration of bepotastine besilate is 4.00% 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 from 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.
75 . The composition of claim 74 containing AVICEL® CL-611 and polysorbate 80 and having pH 6.4, or containing HPMC E15 LV, citric acid monohydrate, and a taste making agent and having pH 6.8.
76 . A kit comprising a metered dose plunger spray pump coupled with a container containing the composition of claim 59 , and instructions for administering the composition using the metered dose plunger spray pump.
77 . The kit of claim 76 wherein the composition is formulated as a nasal spray, nasal drops, nasal droplets, or combinations thereof.
78 . A pharmaceutical composition comprising a pharmaceutically acceptable salt of bepotastine, 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).
79 . A pharmaceutical composition comprising a pharmaceutically acceptable salt of bepotastine, dibasic sodium phosphate heptahydrate, sodium chloride, edetate disodium, benzalkonium chloride, hydroxypropylmethyl cellulose (HPMC), citric acid monohydrate, and a taste making agent.
80 . The pharmaceutical composition of claim 78 wherein the concentration of bepotastine besilate is 4.00% 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.
81 . The pharmaceutical composition of claim 79 wherein the concentration of bepotastine besilate is 4.00% 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.
82 . The composition of claim 78 having pH 6.4.
83 . The composition of claim 79 having pH 6.8.