Taste-masked pharmaceutical compositions

• US 10,130,580 B2
• Filed: 04/20/2018
• Issued: 11/20/2018
• Est. Priority Date: 10/12/2004
• Status: Active Grant

• Current Assignee: Adare Pharmaceuticals, Inc.
• Original Assignee: Adare Pharmaceuticals, Inc.
• Inventors: Venkatesh, Gopi M.
• Primary Examiner(s): Bredefeld, Rachael E
• Application Number:
  US15/958,512
• Publication Number:
  US 20180235877A1
• Time in Patent Office: 214 Days
• CPC Class Codes: A61K 9/0056 Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
• CPC Class Codes: A61K 9/2077 Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets

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 T_max). A process for preparing such compositions for oral administration using conventional fluid-bed equipment and rotary tablet press is also disclosed.

Claims

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 ethylcellulose and the gastrosoluble polymer is an aminoalkyl methacrylate copolymer;

wherein the weight ratio of the water-insoluble polymer to the gastrosoluble polymer in the taste-masking membrane is about 50/50, and the taste-masking membrane thickness ranges from about 10% to 30% by weight of the coated particle,

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 0.1 N HCl at pH 1.2; 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.

2. The pharmaceutical composition of claim 1 comprising one or more drug(s) present in sufficient quantities to be administered orally to a patient in need thereof at a prescribed dosing regimen to provide therapeutic efficacy.

3. The pharmaceutical composition of claim 1 wherein the sugar alcohol or saccharide to disintegrant weight ratio is about 95/5.

4. The pharmaceutical composition of claim 1, wherein the ratio of rapidly-dispersing microgranules to taste-masked particles ranges from about 2/1.

5. The pharmaceutical composition of claim 1, wherein the rapidly-dispersing microgranules comprise a disintegrant selected from the group consisting of crosslinked polyvinylpyrrolidone, sodium starch glycolate, crosslinked sodium carboxymethylcellulose, low-substituted hydroxypropylcellulose and mixtures thereof.

6. The pharmaceutical composition of claim 1, wherein the rapidly-dispersing microgranules comprise (i) the disintegrant crosslinked polyvinylpyrrolidone and (ii) the sugar alcohol mannitol.

7. The pharmaceutical composition of claim 1, wherein the average particle size of the drug-containing core particle is not more than about 400 μ

m.

8. The pharmaceutical composition of claim 1, wherein said orally disintegrating tablet has a friability of not more than about 1%.

9. The pharmaceutical composition of claim 1, wherein said orally disintegrating tablet disintegrates on contact with the saliva in the oral cavity within approximately 60 seconds.

10. The pharmaceutical composition of claim 1, wherein the rapidly dispersing microgranules comprise a sugar alcohol or a saccharide selected from the group consisting of mannitol.

11. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition exhibits acceptable taste-masking when placed in the oral cavity for 60 seconds.

12. The pharmaceutical composition of claim 1, wherein the rapidly dispersing microgranules have an average particle size of not more than 300 μ

m.