Galantamine formulations
Galantamine formulations substantially free of microcrystalline cellulose, lactose, and/or starch are described.
1 . A pharmaceutical solid dosage formulation, comprising:
galantamine or a pharmaceutically acceptable salt thereof; and
a pharmaceutically acceptable excipient, with the proviso that the formulation does not contain microcrystalline cellulose; and
wherein the formulation exhibits a dissolution profile such that after 10 minutes at least about 90% of the galantamine or galantamine salt is released after combining the dosage formulation with 500 ml of purified water at 37° C. in Apparatus 2 (USP, <711> Dissolution, paddle, 50 rpm).
2 . The formulation of claim 1 , wherein the galantamine salt is galantamine hydrobromide.
3 . The formulation of claim 1 , wherein the excipient is selected from the group consisting of lactose-based material; cellulosic material, excluding microcrystalline cellulose; starch; sugar; sugar alcohol; saccharide; polysaccharide; dibasic calcium phosphate, calcium sulfate, and combinations thereof.
4 . The formulation of claim 1 , further comprising a disintegrant.
5 . The formulation of claim 4 , wherein the disintegrant is selected from the group consisting of partially pregelatinized starch, pregelatinized starch, polyvinylpyrrolidone, croscarmellose, croscarmellose sodium, sodium starch glycolate, crospovidone, and combinations thereof.
6 . The formulation of claim 1 , wherein the formulation provides an AUC after administration that is more than 80 percent and less than 120 percent of the AUC provided between 0 and 24 hours after administration by the same strength dosage form of galantamine hydrobromide
wherein the same strength dosage form of galantamine hydrobromide comprises colloidal silicon dioxide in a weight ratio to galantamine hydrobromide of about 0.0234:1,
crospovidone in a weight ratio to galantamine hydrobromide of about 0.585:1,
hydroxypropyl methylcellulose in a weight ratio to galantamine hydrobromide of about 0.488:1,
lactose monohydrate in a weight ratio to galantamine hydrobromide of about 7.53:1,
magnesium stearate in a weight ratio to galantamine hydrobromide of about 0.0585:1,
microcrystalline cellulose in a weight ratio to galantamine hydrobromide of about 2.51:1,
propylene glycol in a weight ratio to galantamine hydrobromide of about 0.188:1,
talc in a weight ratio to galantamine hydrobromide of about 0.0975:1, and titanium dioxide in a weight ratio to galantamine hydrobromide of about 0.146:1.
7 . A tablet comprising the formulation of claim 1 .
8 . The tablet of claim 7 , further comprising a film coating disposed on the surface of the tablet.
9 . A pharmaceutical solid dosage formulation, comprising:
galantamine or a pharmaceutically acceptable salt thereof; and
a pharmaceutically acceptable excipient,
with the proviso that the solid dosage formulation, excluding an optional coating disposed on the solid dosage formulation,
i) does not contain a cellulosic material, or
ii) does not contain starch.
10 . The formulation of claim 9 , wherein the galantamine salt is galantamine hydrobromide.
11 . The formulation of claim 9 , wherein the excipient is selected from the group consisting of lactose-based material; sugar; sugar alcohol; saccharide; polysaccharide; dibasic calcium phosphate, calcium sulfate, and combinations thereof.
12 . The formulation of claim 9 , further comprising a disintegrant.
13 . The formulation of claim 12 , wherein the disintegrant is selected from the group consisting of polyvinylpyrrolidone, croscarmellose, croscarmellose sodium, crospovidone, and combinations thereof.
14 . A tablet comprising the formulation of claim 9 .
15 . An immediate release solid pharmaceutical dosage formulation, comprising:
galantamine or a pharmaceutically acceptable salt thereof; and
a pharmaceutically acceptable excipient, with the proviso that the formulation does not contain a lactose-based material and wherein the formulation is directly compressible.
16 . The formulation of claim 15 , wherein the galantamine salt is galantamine hydrobromide.
17 . The formulation of claim 16 , wherein the excipient is selected from the group consisting of cellulosic material, excluding microcrystalline cellulose; starch; sugar; sugar alcohol; saccharide; polysaccharide; dibasic calcium phosphate, calcium sulfate, and combinations thereof.
18 . The formulation of claim 15 , further comprising a disintegrant.
19 . A tablet comprising the formulation of claim 15 .
20 . A process of preparing a pharmaceutical solid dosage formulation, comprising:
blending galantamine or a pharmaceutically acceptable salt thereof with an excipient and disintegrant to form a preblend;
blending the preblend with a glidant and optional additives to form a blend; and
forming the blend into tablets using direct compression; wherein the solid dosage formulation is free of an excipient selected from the group consisting of microcrystalline cellulose, lactose, starch, and combinations thereof.
21 . The process of claim 20 , further comprising blending the preblend with a an excipient to form an intermediate blend that is then blended with the glidant.
22 . A pharmaceutical solid dosage formulation, comprising:
(a) galantamine hydrobromide;
(b) lactose-based excipient; and
(c) crospovidone, partially pregelatinized maize starch or a combination of the foregoing; and wherein the solid dosage formulation is free of microcrystalline cellulose.
23 . The formulation of claim 22 , wherein the lactose-based excipient comprises lactose impalpable and spray dried lactose monohydrate.
24 . A tablet comprising the formulation of claim 22 .
25 . A method of treating a patient with Alzheimer's disease, comprising orally administering a therapeutically effective amount of the formulation of claim 1 to a patient.
26 . A method of treating a patient with Alzheimer's disease, comprising orally administering a therapeutically effective amount of the formulation of claim 9 to a patient.
27 . A method of treating a patient with Alzheimer's disease, comprising orally administering a therapeutically effective amount of the formulation of claim 15 to a patient.
28 . A method of treating a patient with Alzheimer's disease, comprising orally administering a therapeutically effective amount of the formulation of claim 22 to a patient.