METHOD OF MANUFACTURING AN ORALLY DISINTIGRATING TABLET
An orally disintegrating composition having a bimodal particle size distribution, methods for its production and use thereof are provided.
1 . A method of manufacturing an orally disintegrating tablet comprising a plurality of compressed particles having a bimodal size distribution comprising a first and a second population of particles, the method comprising the steps of:
(i) applying a solution or dispersion comprising a drug coating layer to a plurality of inert seeds thereby generating a plurality of cores, wherein the drug coating layer comprises a proton pump inhibitor, an alkalizing agent, a binder, a surfactant, and a filler;
(ii) applying a solution or dispersion comprising a subcoating layer to the plurality of cores thereby generating a plurality of subcoated cores, wherein the subcoating layer comprises a binder, an anti-tacking agent, a surfactant, and a filler;
(iii) applying a solution or dispersion comprising an enteric coating layer to the subcoated cores thereby generating enteric coated cores constituting a first population of particles, wherein the enteric coating layer is the outermost coating layer in said population of particles comprising an enteric polymer, an anti-tacking agent, a plasticizer, a colorant, and optionally an anti-static agent;
(iv) mixing the first population of particles with a second population of particles comprising a mixture of powders comprising a disintegrant and a sugar alcohol; and
(v) compressing the mixture of the first and second populations of particles thereby obtaining the orally disintegrating tablet.
2 . The method of claim 1 , wherein the weight percent ratio of the first population of particles to the second population of particles is about 0.5:1 to about 1:0.5.
3 . The method of claim 1 , wherein the inert seeds comprise sugar spheres; the drug coating layer comprises lansoprazole, meglumine, hydroxypropyl methyl cellulose, mannitol, and polysorbate; the subcoating layer comprises hydroxypropyl methyl cellulose, mannitol, talc, and polysorbate; and the enteric coating layer comprises hydroxypropyl methyl cellulose phthalate, cetyl alcohol, triethyl citrate, talc, and titanium dioxide.
4 . The method of claim 1 , wherein the inert seeds are in an amount of about 2% to about 10%, the drug coating layer is in an amount of about 1% to about 50%, the subcoating layer is in an amount of about 2% to about 30%, and the enteric coating layer is in an amount of about 10% to about 20% by weight of the total mass of the orally disintegrating tablet.
5 . The method of claim 1 , wherein the disintegrant is in an amount of about 2% to about 20% by weight of the total mass of the orally disintegrating tablet, and wherein the weight percent ratio of the sugar alcohol to the disintegrant is at least 2:1.
6 . An orally disintegrating tablet comprising a plurality of compressed particles having a bimodal size distribution comprising a first and a second population of particles, wherein the first population of particles comprises:
a) inert seeds comprising a filler;
b) a drug coating layer over the inert seeds, the drug coating layer comprising a proton pump inhibitor, an alkalizing agent, a binder, a surfactant, and a filler;
c) a subcoating layer over the drug coating layer, the subcoating layer comprising a binder, an anti-tacking agent, a surfactant, and a filler; and
d) an enteric coating over the subcoating layer, the enteric coating comprising an enteric polymer, an anti-tacking agent, a plasticizer, a colorant, and optionally an anti-static agent, wherein the enteric coating layer is the outermost coating layer in said population; and
wherein the second population of particles comprises a mixture of powders comprising a disintegrant and a sugar alcohol.
7 . The orally disintegrating tablet of claim 6 , wherein the ratio of the median particle size of the first population of particles to the median particle size of the second population of particles is about 2:1 to about 5:1, wherein the first population of particles has a median particle size in the range of about 400 μm to about 600 μm and the second population of particles has a median particle size in the range of about 50 μm to about 250 μm.
8 . The orally disintegrating tablet of claim 7 , wherein the first population of particles has a d 10 particle size in the range of about 300 μm to about 500 μm, and wherein the second population of particles has a d 10 particle size in the range of about 1 μm to about 100 μm.
9 . The orally disintegrating tablet of claim 7 , wherein the first population of particles has a d 90 particle size in the range of about 500 μm to about 700 μm, and wherein the second population of particles has a d 90 particle size in the range of about 250 μm to about 500 μm.
10 . The orally disintegrating tablet of claim 6 , wherein the weight percent ratio of the first population of particles to the second population of particles is about 0.5:1 to about 1:0.5.
11 . The orally disintegrating tablet of claim 6 , wherein the proton pump inhibitor comprises lansoprazole, omeprazole, pantoprazole, leminoprazole, perprazole, rabeprazole, or a pharmaceutically acceptable salt thereof, and a mixture or combination thereof.
12 . The orally disintegrating tablet of claim 6 , wherein the inert seeds comprise sugar spheres.
13 . The orally disintegrating tablet of claim 6 , wherein the drug coating layer comprises lansoprazole, meglumine, hydroxypropyl methyl cellulose, mannitol, and polysorbate.
14 . The orally disintegrating tablet of claim 6 , wherein the subcoating layer comprises hydroxypropyl methyl cellulose, mannitol, talc, and polysorbate.
15 . The orally disintegrating tablet of claim 6 , wherein the enteric coating layer comprises hydroxypropyl methyl cellulose phthalate, cetyl alcohol, triethyl citrate, talc, and titanium dioxide.
16 . The orally disintegrating tablet of claim 6 comprising inert seeds in an amount of about 2% to about 10%, a drug coating layer in an amount of about 1% to about 50%, a subcoating layer in an amount of about 2% to about 30%, and an enteric coating layer in an amount of about 10% to about 20% by weight of the total mass of the orally disintegrating tablet.
17 . The orally disintegrating tablet of claim 6 , wherein the disintegrant is in an amount of about 2% to about 20% by weight of the total mass of the orally disintegrating tablet.
18 . The orally disintegrating tablet of claim 6 , wherein the weight percent ratio of the sugar alcohol to the disintegrant is at least 2:1.
19 . A method of inhibiting gastric acid secretion, the method comprising administering to a subject in need thereof the orally disintegrating tablet of claim 6 .
20 . A method of treating a disease or disorder selected from the group consisting of gastroesophageal reflux disease, gastritis, peptic ulcers (duodenal and gastric) and erosive esophagitis, the method comprising administering to a subject in need thereof the orally disintegrating tablet of claim 6 .