TASTE-MASKED PHARMACEUTICAL COMPOSITIONS PREPARED BY COACERVATION

• US 20090263480A1
• Filed: 05/15/2009
• Published: 10/22/2009
• Est. Priority Date: 11/12/2004
• Status: Abandoned Application

• Current Assignee: Adare Pharmaceuticals, Inc.
• Original Assignee: Adare Pharmaceuticals, Inc.
• Inventors: Qian, Ken Kangyi, Venkatesh, Gopi M., Lai, Jin-Wang
• Application Number:
  US12/466,855
• Publication Number:
  US 20090263480A1
• Time in Patent Office: Days
• US Class Current: 424/465
• CPC Class Codes: A61K 31/4045 Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
• CPC Class Codes: A61K 31/495 having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazinesA61K31/48 takes precedence ; with three nitrogen atoms A61K31/53
• 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 9/1676 having a drug-free core with discrete complete coating layer containing drug adsorbates of liquid drug formulations on inert powders without simultaneous granulation step A61K9/141; with further drug-free outer coating A61K9/5078; drug conjugated to non-active particles A61K47/6921
• CPC Class Codes: A61K 9/2077 Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

There is provided a method for preparing an orally disintegrating tablet (ODT) composition comprising microparticles of one or more taste-masked active pharmaceutical ingredients, rapidly-dispersing microgranules, and other optional, pharmaceutically acceptable excipients wherein the ODT disintegrates rapidly with saliva in the buccal cavity forming a smooth, easy-to-swallow suspension. Furthermore, the microparticles (crystals, granules, beads or pellets containing one or more actives) with a taste-masking membrane applied by a modified solvent coacervation process comprising a water-insoluble polymer and at least one gastrosoluble inorganic or organic pore-former, exhibit a pleasant taste when placed in the oral cavity and provide rapid, substantially-complete release of the dose on entry into the stomach.

Claims

1. An orally disintegrating tablet comprising:

taste-masked microparticles comprising one or more active pharmaceutical ingredients; and

rapidly-dispersing microgranules comprising a disintegrant and a sugar alcohol or saccharide, or a mixture thereof;

wherein;

the taste-masked microparticles comprise a taste-masking membrane disposed on crystals of an antiepileptic drug; and

the sugar alcohol or saccharide have an average particle size of not more than about 30 μ

m.

2. The orally disintegrating tablet of claim 1, wherein not less than 75% of the antiepileptic drug is released in 30 minutes when tested for dissolution using United States Pharmacopoeia Apparatus 1 (baskets@100 rpm) or Apparatus (paddles at 50 rpm) in 900 mL of 0.1N HCl.

3. The orally disintegrating tablet of claim 1, wherein the orally disintegrating tablet composition disintegrates on contact with saliva in about 60 seconds, thereby forming a smooth suspension.

4. The orally disintegrating tablet of claim 1, wherein the amount of taste-masking membrane is about 5% to about 50% of the total weight of the taste-masked microparticles.

5. The orally disintegrating tablet of claim 1, wherein the average particle size of the taste-masked microparticles is not more than about 400 μ

m.

6. The orally disintegrating tablet of claim 1, wherein the average particle size of the taste-masked microparticles is not more than about 300 μ

m.

7. The orally disintegrating tablet of claim 1, wherein the average particle size of the taste-masked microparticles is not more than about 200 μ

m.

8. The orally disintegrating tablet of claim 1, wherein the taste-masked microparticles release not more than about 10% of the antiepileptic drug in about 3 minutes in the buccal cavity of a patient.

9. The orally disintegrating tablet of claim 1, wherein the taste-masking membrane comprises a water-insoluble polymer.

10. The orally disintegrating tablet of claim 9, wherein the water-insoluble polymer is selected from the group consisting of ethylcellulose, polyvinyl acetate, cellulose acetate, cellulose acetate butyrate, and methacrylate copolymers.

11. The orally disintegrating tablet of claim 1, further comprising pharmaceutically acceptable fillers and diluents.

12. The orally disintegrating tablet of claim 1, wherein the ratio of disintegrant to sugar alcohol or saccharide ranges from about 90/10 to about 95/5.

13. The orally disintegrating tablet of claim 1, wherein the disintegrant is selected from the group consisting of crospovidone, sodium starch glycolate, crosslinked sodium carboxymethyl cellulose, low substituted hydroxypropyl cellulose, and mixtures thereof.

14. The orally disintegrating tablet of claim 1, wherein the sugar alcohol or saccharide is selected from the group consisting of lactose, mannitol, sorbitol, xylitol, maltitol, and mixtures thereof.

15. The orally disintegrating tablet of claim 1, further comprising additional disintegrant separate from the rapidly dispersing microgranules.

16. The orally disintegrating tablet of claim 1, wherein:

the amount of taste-masking membrane is about 5% to about 50% of the total weight of the taste-masked microparticles;

the average particle size of the taste-masked microparticles is not more than about 400 μ

m;

the taste-masking membrane comprises ethyl cellulose; and

the disintegrant comprises crospovidone.

17. The orally disintegrating tablet of claim 16, further comprising additional disintegrant separate from the rapidly dispersing microgranules.