Taste masking of highly water-soluble drugs

• US 20030096791A1
• Filed: 05/30/2002
• Published: 05/22/2003
• Est. Priority Date: 05/31/2001
• Status: Abandoned Application

• Current Assignee: Cima Labs Incorporated (Teva Pharmaceutical Industries Limited)
• Original Assignee: Cima Labs Incorporated (Teva Pharmaceutical Industries Limited)
• Inventors: Holt, Kris E., Gupte, Vijay V., Habib, Walid, Khankari, Rajendra K., Hontz, John
• Application Number:
  US10/158,715
• Publication Number:
  US 20030096791A1
• Time in Patent Office: Days
• US Class Current: 514/57
• 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 31/716 Glucans
• 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 9/5078 with drug-free core

Abstract

A taste-masked formulation which provides for effective taste-masking of an active ingredient such as cetirizine hydrochloride, while simultaneously providing a desired dissolution profile.

Claims

1. A taste-masked formulation comprising:

taste-masked particles including (1) at least one active ingredient and (2) a taste-masking layer surrounding said at least one active ingredient, said taste-masking layer including from about 2% to about 20% of a water-soluble polymer and from about 80% to about 98% of a water-insoluble polymer, said water-insoluble polymer being selected from the group consisting of ethyl cellulose, cellulose acetate phthalate, hydroxypropyl methyl cellulose phthalate, polyvinyl acetate phthalate, hydroxypropyl methyl cellulose succinate, and shellac, and wherein said taste-masking layer has a coating thickness from about 2% to about 100% by weight, based on the weight of said taste-masked particles, wherein said taste-masked formulation releases less than about 20% of the at least one active ingredient in an aqueous solution at a basic pH in about 3 minutes and releases at least about 65% of said at least one active ingredient at an acidic pH in about 30 minutes.

2. The taste-masked formulation of claim 1, wherein said release is less than about 16% of the at least one active ingredient in an aqueous solution at a neutral to basic pH in about 3 minutes and releases at least about 75% of said at least one active ingredient at an acidic pH in about 30 minutes.

3. The taste-masked formulation of claim 1, wherein said water-soluble polymer is selected from the group consisting of hydroxypropyl methyl cellulose, polyvinyl pyrrolidone, polyvinyl alcohol, hydroxypropyl cellulose, hydroxyethyl cellulose, methyl cellulose, carboxymethyl cellulose, and polyethylene glycols.

4. The taste-masked formulation of claim 1, wherein said taste-masking layer includes from about 5% to about 15% of said water-soluble polymer and from about 85% to about 95% of said water-insoluble polymer.

5. The taste-masked formulation of claim 1, wherein said taste-masking layer includes from about 10% to about 15% of said water-soluble polymer and from about 85% to about 90% of said water-insoluble polymer.

6. The taste-masked formulation of claim 1, wherein said taste-masking layer is provided in an amount from about 25% to about 100% of the taste-masked particles by weight.

7. The taste-masked formulation of claim 1, wherein said taste-masking layer is provided in an amount from about 30% to about 100% of the taste-masked particles by weight.

8. The taste-masked formulation of claim 1, further comprising a solid support in intimate contact with said active ingredient.

9. The taste-masked formulation of claim 1, wherein said solid support is in the form of particles.

10. The taste-masked formulation of claim 9, wherein said particles are in the form of beads, or spheres.

11. The taste-masked formulation of claim 9, wherein the particles are in the form of spheres which are selected from the group consisting of sugar spheres, microcrystalline cellulose spheres.

12. The taste-masked formulation of claim 1, further comprising a binder which facilitates the binding of said active ingredient onto said solid support.

13. The taste-masked formulation of claim 1, wherein said at least one active ingredient has a water solubility of about 0.03 g/ml or more.

14. The taste-masked formulation of claim 1, wherein said at least one active ingredient has a water solubility of at least 1.0 g/ml at room temperature.

15. The taste-masked formulation of claim 1, wherein said at least one active ingredient has a water solubility of at least 1.5 g/ml at room temperature.

16. The taste-masked formulation of claim 1, wherein said at least one active ingredient has a water solubility of at least 1.6 g/ml at room temperature.

17. The taste-masked formulation of claim 1, wherein said at least one active ingredient is selected from the group consisting of cetirizine hydrochloride and pseudoephedrine.

18. The taste-masked formulation of claim 12, wherein said binder is selected from the group consisting of:

hydroxypropyl methylcellulose, HPMC, polyvinyl pyrrolidone, starch, gum arabic, carboxymethylcellulose, polyvinylpyrrolidone, hydroxypropylcellulose, crystalline cellulose, sucrose, D-mannitol, dextrin, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, polyvinylpyrrolidone, povidone, acacia, tragacanth, gelatin, cellulose materials, alginic acids and salts thereof, magnesium aluminum silicate, polyethylene glycol, guar gum, polysaccharide acids, bentonites, sugars, and invert sugars.

19. The taste-masked formulation of claim 16, wherein the cellulose materials are methyl cellulose or sodium carboxy methyl cellulose.

20. The taste-masked formulation of claim 1, wherein said formulation further comprises at least one pharmaceutically acceptable excipient.

21. A pharmaceutical dosage form comprising a taste-masked formulation which includes:

taste-masked particles including (1) at least one active ingredient and (2) a taste-masking layer surrounding said at least one active ingredient, said taste-masking layer including from about 2% to about 20% of a water-soluble polymer and from about 80% to about 98% of a water-insoluble polymer, said water-insoluble polymer being selected from the group consisting of ethyl cellulose, cellulose acetate phthalate, hydroxypropyl methyl cellulose phthalate, polyvinyl acetate phthalate, hydroxypropyl methyl cellulose succinate, and shellac, and wherein said taste-masking layer is provided in an amount of at least 10% of said taste-masked particles by weight, wherein said taste-masked formulation releases less than about 20% of the at least one active ingredient in an aqueous solution at a basic pH in about 3 minutes and releases at least about 65% of said at least one active ingredient at an acidic pH in about 30 minutes.

22. The pharmaceutical dosage form of claim 21, wherein said dosage form is selected from the group consisting of orally disintegrating tablet, orally disintegrating capsule, soft gel capsule, caplet, slugged capsule, and chewable tablet.

23. The pharmaceutical dosage form of claim 21, further comprising at least one pharmaceutically acceptable excipient.

24. The pharmaceutical dosage form of claim 22, further comprising a binder, a filler, a lubricant, a disintegrant, a bulking agent, a color, a solvent, a flavor adsorbent or a flavor absorbent.

25. The pharmaceutical dosage form of claim 21, wherein said pharmaceutically acceptable excipient is used in an amount from about 5% to about 90% by weight based on the weight of the dosage form.

26. The pharmaceutical dosage form of claim 21, wherein the at least one active ingredient is present in an amount from about 0.1 mg to about 1000 mg per dosage.

27. The pharmaceutical dosage form of claim 26, wherein the at least one active ingredient is present in an amount from about 1 mg to about 500 mg per dosage.

28. The pharmaceutical dosage form of claim 26, wherein the at least one active ingredient is present in an amount from about 4 mg to about 200 mg per dosage.

29. The pharmaceutical dosage form of claim 26, wherein said taste-masking layer is provided in an amount from about 10% to about 100% of said taste-masked particles by weight.

30. The pharmaceutical dosage form of claim 25, wherein the at least one active ingredient is present in an amount from about 0.1 mg to about 1000 mg per dosage.