Taste-masked pharmaceutical compositions
First Claim
1. A pharmaceutical composition comprising:
- (1) a plurality of taste-masked particles, wherein each taste-masked particle comprises;
(a) a drug-containing core particle;
(b) a taste-masking membrane disposed on said drug-containing core particle comprising a combination of a water-insoluble polymer and a gastrosoluble polymer, wherein the water-insoluble polymer is selected from the group consisting of ethylcellulose, polyvinyl acetate, cellulose acetate, cellulose acetate phthalate, cellulose acetate butyrate, methacrylate copolymers and combinations thereof, and the gastrosoluble polymer is selected from the group consisting of maltodextrin, aminoalkyl methacrylate copolymer, polyvinylacetate diethylaminoacetate, and combinations thereof;
wherein the ratio of the water-insoluble polymer to the gastrosoluble polymer in the taste-masking membrane ranges from about 95/5 to about 65/35 and the pharmaceutical composition releases greater than or equal to about 60% of the total amount of drug in 30 minutes when tested for dissolution using United States Pharmacopoeia Apparatus 2 using paddles at 50 rpm in 900 mL of pH 1.2 buffer; and
wherein said taste-masked particles release not more than about 10% of the total amount of drug in about 3 minutes when dissolution tested in simulated saliva fluid at pH about 6.8; and
(2) a plurality of rapidly-dispersing microgranules having an average particle size of not more than about 400 μ
m comprising (i) a disintegrant and (ii) a sugar alcohol or a saccharide or a combination thereof, wherein each of said disintegrant and sugar alcohol or saccharide is present in the form of particles having an average particle diameter of not more than about 30 μ
m, and wherein the pharmaceutical composition is an orally disintegrating tablet.
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Accused Products
Abstract
There is provided a method for preparing an orally disintegrating tablet (ODT) composition comprising microparticles of one or more taste-masked active pharmaceutical ingredient(s), rapidly-dispersing microgranules, and other optional, pharmaceutically acceptable excipients wherein the ODT disintegrates on contact with saliva in the buccal cavity in about 60 seconds forming a smooth, easy-to-swallow suspension. Furthermore, the microparticles (crystals, granules, beads or pellets containing the active) applied with a taste-masking membrane comprising a combination of water-insoluble and gastrosoluble polymers release not less than about 60% of the dose is in the stomach in about 30 minutes, thus maximizing the probability of achieving bioequivalence to the reference IR product having rapid onset of action (short Tmax). A process for preparing such compositions for oral administration using conventional fluid-bed equipment and rotary tablet press is also disclosed.
236 Citations
27 Claims
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1. A pharmaceutical composition comprising:
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(1) a plurality of taste-masked particles, wherein each taste-masked particle comprises; (a) a drug-containing core particle; (b) a taste-masking membrane disposed on said drug-containing core particle comprising a combination of a water-insoluble polymer and a gastrosoluble polymer, wherein the water-insoluble polymer is selected from the group consisting of ethylcellulose, polyvinyl acetate, cellulose acetate, cellulose acetate phthalate, cellulose acetate butyrate, methacrylate copolymers and combinations thereof, and the gastrosoluble polymer is selected from the group consisting of maltodextrin, aminoalkyl methacrylate copolymer, polyvinylacetate diethylaminoacetate, and combinations thereof;
wherein the ratio of the water-insoluble polymer to the gastrosoluble polymer in the taste-masking membrane ranges from about 95/5 to about 65/35 and the pharmaceutical composition releases greater than or equal to about 60% of the total amount of drug in 30 minutes when tested for dissolution using United States Pharmacopoeia Apparatus 2 using paddles at 50 rpm in 900 mL of pH 1.2 buffer; and
wherein said taste-masked particles release not more than about 10% of the total amount of drug in about 3 minutes when dissolution tested in simulated saliva fluid at pH about 6.8; and(2) a plurality of rapidly-dispersing microgranules having an average particle size of not more than about 400 μ
m comprising (i) a disintegrant and (ii) a sugar alcohol or a saccharide or a combination thereof, wherein each of said disintegrant and sugar alcohol or saccharide is present in the form of particles having an average particle diameter of not more than about 30 μ
m, and wherein the pharmaceutical composition is an orally disintegrating tablet. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18)
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19. A method of manufacturing a pharmaceutical composition comprising:
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(a) preparing core particles comprising a drug; and (b) coating the core particles by applying a membrane comprising a mixture of water-insoluble polymer and a gastrosoluble polymer wherein the water-insoluble polymer is selected from the group consisting of ethylcellulose, polyvinyl acetate, cellulose acetate, cellulose acetate phthalate, cellulose acetate butyrate, methacrylate copolymers and combinations thereof and the gastrosoluble polymer is selected from the group consisting of maltodextrin, aminoalkyl methacrylate copolymer, polyvinylacetate diethylaminoacetate, and combinations thereof;
wherein the ratio of the water-insoluble polymer to the gastrosoluble polymer in the taste-masking membrane ranges from about 95/5 to about 65/35;(c) granulating particles of a sugar alcohol and/or a saccharide, each particle of sugar alcohol and/or saccharide having an average particle diameter of not more than 30 μ
m, with a disintegrant having an average particle diameter of not more than 30 μ
m to produce rapidly-dispersing microgranules with an average particle size of not more than about 400 μ
m;(d) blending the membrane coated microparticles of step (b) with the rapidly-dispersing microgranules of step (c) at a ratio of about ⅙
to about ½
; and(e) compressing the blend of step (d) into orally disintegrating tablets. - View Dependent Claims (20, 21, 22, 23, 24, 25, 26, 27)
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Specification