Galantamine formulations
Galantamine formulations, including sustained-release and fast dissolve formulations, are described.
1 . (canceled)
2 . A dosage formulation, comprising:
galantamine or a pharmaceutically acceptable salt, hydrate, solvate, crystal form, diastereomer, prodrug, or mixture thereof; and
a pharmaceutically acceptable carrier; and
wherein the formulation exhibits a dissolution profile such that after 0.5 hour loss than about 75% of the galantamine or galantamine salt is released after combininig the dosage formulation with 500 ml or purified water at 37° C. in Apparatus 2 (USP, <711 > Dissolution, paddle, 50 rpm).
3 . The formulation of claim 2 , wherein the galantamine salt is galantamine hydrobromide.
4 .- 6 . (canceled)
7 . The formulation of claim 2 , further comprising a cognition enhancer, an anti-emetic, a proton-pump inhibitor, an antacid, or a combination comprising at least one of the foregoing.
8 . The formulation of claim 7 , wherein the cognition enhancer is memantine, metrifonate, rivastigmine, tacrine, a pharmaceutically acceptable salt thereof or a combination comprising at least one of the foregoing cognition enhancers.
9 . The formulation of claim 7 , wherein the anti-emetic is dolasetron mesylate, ondansetron, metoclopramide, granisetron, prochlorperazine, a pharmaceutically acceptable salt thereof, or a combination comprising at least one of the foregoing anti-emetics.
10 . The formulation of claim 7 , wherein the antacid is aluminum hydroxide, magnesium, hydroxide, aluminum carbonate, calcium carbonate, sodium bicarbonate, or a combination comprising at least one of the foregoing antacids.
11 . The formulation of claim 7 , wherein the proton pump inhibitor is omeprazole, esomeprazole magnesium, lansoprazole, esomeprazole, pantoprazole, rabeprazole, or a combination comprising at least one of the foregoing proton pump inhibitors.
12 . (canceled)
13 . The formulation of claim 2 , wherein the formulation provides bioequivalence according to FDA guidelines or criteria.
14 . (canceled)
15 . A sustained-release formulation, comprising:
galantamine or a pharmaceutically acceptable salt, hydrate, solvate, crystal form, diastereomer, prodrug, or mixture thereof; and
a release-retarding material, wherein the release-retarding material is all acrylate polymer, wax, modified cellulose, shellac, zein, hydrogenated vegetable oil, hydrogenated castor oil, or combinations comprising at least one of the foregoing release-retarding materials,
wherein the formulation exhibits a dissolution profile such that less than about 18% of the galantamine is released in 1 hour, and less than about 80% of the galantamine is released in 10 hours after combining the formulation with a dissolution medium at 37° C. in Apparatus 2 (USP, <711> Dissolution, paddle, 50 rpm).
16 . The sustained-release formulation of claim 15 , wherein the salt is galantamine hydrobromide.
17 . The sustained-release formulation of claim 15 , wherein the acrylate polymer is a methyl methacrylate copolymer, an ethoxyethyl methacrylate, a cyanoethyl methacrylate, an aminoalkyl methacrylate copolymer, a poly(acrylic acid), a poly(methacrylic acid), a methacrylic acid alkylamide copolymer, a poly(methyl methacrylate), a poly(methacrylic acid anhydride), a methyl methacrylate, a polymethacrylate, a poly(methyl methacrylate) copolymer, a polyacrylamide, an aminoalkyl methacrylate copolymer, a glycidyl methacrylate copolymer, an ammonio methacrylate copolymer, or a combination comprising at least one of the foregoing acrylate polymers.
18 . The sustained-release formulation of claim 15 , wherein the modified cellulose is an alkyl cellulose, a hydroxyalkyl cellulose, or a combination comprising at least one of the foregoing modified celluloses.
19 . The sustained-release formulation of claim 15 , wherein the alkyl cellulose is methyl cellulose, ethyl cellulose, or a combination comprising at least one of the foregoing alkyl celluloses.
20 . The sustained-release formulation of claim 15 , wherein the hydroxyalkyl cellulose is hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, hydroxypropylethylcellulose, hydroxypropylpropylcellulose, hydroxypropylbutylcellulose or a combination comprising at least one of the foregoing hydroxyalkyl celluloses.
21 . The sustained-release formulation of claim 15 , wherein the release-retarding material is in the form of a coating.
22 . The sustained-release formulation of claim 21 , wherein the coating comprises a water insoluble polymer.
23 . The sustained-release formulation of claim 21 , wherein the coating comprises an aqueous dispersion of a water insoluble polymer.
24 .- 38 . (canceled)
39 . The dosage formulation of claim 15 ,
wherein the dosage formulation exhibits a dissolution profile such that
after 1 hour about 5 to about 15% of the galantamine or galantamine salt is released,
after 2 hours about 10 to about 25% of galantamine or galantamine salt is released,
after 4 hours about 15 to about 35% of the galantamine or galantainine salt is released, and
after 8 hours about 25 to about 50% of galantamine or galantamine salt is released.
40 .- 50 . (canceled)
51 . The dosage formulation of claim 15 , wherein the dissolution medium is 500 ml of purified water.
52 . The dosage formulation of claim 15 , wherein the dissolution medium is 500 ml of an aqueous buffer solution (USP, p11 4.5); an aqueous buffer solution (USP, p11 6.8); an aqueous buffer solution (USP, pH 7.5); or 0.1N HCl.