Edible oral strip or wafer dosage form containing ion exchange resin for taste masking

Patent metadata

Field	Value
Publication number	US-10744176-B2
Application number	US-201916511236-A
Country	US
Kind code	B2
Filing date	Jul 15, 2019
Priority date	Jun 8, 2011
Publication date	Aug 18, 2020
Grant date	Aug 18, 2020

Abstract

An edible orally disintegrating tablet dosage form containing an unpalatable acidic active pharmaceutical ingredient, particularly ketoprofen, and an ion exchange resin as a primary taste masking agent, along with an optional alkaline agent and further optionally containing one or more secondary taste masking agents is provided. The edible orally disintegrating tablet dosage matrix is formed from at least one water soluble or miscible polymer(s). The optional secondary taste masking ingredients include one or more of flavoring agent(s), sweetener(s), cooling sensation agent(s), and taste receptor blocker(s). The inventive dosages minimize or completely mask the bitterness, burning sensation and throat irritation associated with many acidic active pharmaceutical ingredients. Methods for preparing the inventive edible oral film strip dosage forms are disclosed, as well as their method of administration.

First claim

The invention claimed is:

1. An edible orally disintegrating tablet comprising at least one water dispersible or water disintegrable polymer, an acidic active pharmaceutical ingredient and at least one anion exchange resin as a primary taste masking agent, wherein said tablet further comprises an edible alkaline agent in an amount that is less than or equal to the amount of active ingredient; wherein said edible alkaline agent imparts gastric release of said acidic active pharmaceutical ingredient.

2. An edible orally disintegrating tablet as claimed in claim 1 , wherein said alkaline agent is selected from hydroxides, edible bicarbonates, edible carbonates, basic amino acids, buffers and mixtures thereof.

3. An edible orally disintegrating tablet as claimed in claim 1 , wherein said tablet further comprises one or more secondary taste masking agents.

4. An edible orally disintegrating tablet as claimed in claim 3 , wherein the secondary taste masking agents are selected from one or more of sweetener(s), flavoring agent(s), cooling sensation agent(s), and taste receptor blocker(s); said primary taste masking agent reduces or eliminates the unpleasant taste and burning sensation associated with the acidic active ingredient and said secondary taste masking agents block any residual unpleasant taste, burning sensation and/or throat irritation associated with the active pharmaceutical ingredient.

5. An edible orally disintegrating tablet as claimed in claim 4 , wherein said secondary taste masking agent comprises at least one sweetener selected from dextrose, lactose, fructose, mannitol, sucrose, trehalose, sucralose, xylitol, mannitol, aspartame, saccharin, sorbitol, sodium saccharin, sodium cyclamate, acesulfame, honey, isomalt, maltodextrin, dextrin, dextrates.

6. An edible orally disintegrating tablet as claimed in claim 3 , wherein said secondary taste masking agent includes a sweetener composition comprising isomalt and a sweetener selected from one or more of sucralose, aspartame, saccharine and acesulfame.

7. An edible orally disintegrating tablet as claimed in claim 3 , wherein said secondary taste masking agent includes at least one flavouring agent selected from essential oils or extracts of menthol wintergreen, peppermint, sweet mint, spearmint, vanillin, cherry, butterscotch, chocolate, cinnamon, clove, lemon, orange, raspberry, rose, spice, violet, herbal, fruit, strawberry, grape, pineapple, vanilla, peppermint, peach, kiwi, papaya, mango, coconut, tutti frutti, apple, coffee, plum, watermelon, nuts, green tea, grapefruit, banana, butter, and chamomile.

8. An edible orally disintegrating tablet as claimed in claim 3 , wherein the secondary taste masking agent comprises a cooling sensation agent selected from one or more of essential oils or extracts of menthol, wintergreen, peppermint, sweet mint, spearmint.

9. An edible orally disintegrating tablet as claimed in claim 3 , wherein the secondary taste masking agent comprises PEG-40 Hydrogenated Castor Oil as a taste receptor blocker.

10. An edible orally disintegrating tablet as claimed in claim 4 , wherein said secondary taste masking agent includes at least one flavouring agent selected from essential oils or extracts of menthol, wintergreen, peppermint, sweet mint, spearmint, vanillin, cherry, butterscotch, chocolate, cinnamon, clove, lemon, orange, raspberry, rose, spice, violet, herbal, fruit, strawberry, grape, pineapple, vanilla, peppermint, peach, kiwi, papaya, mango, coconut, tutti fruitti, apple, coffee, plum, watermelon, nuts, green tea, grapefruit, banana, butter, and chamomile.

11. An edible orally disintegrating tablet as claimed in claim 1 , wherein the acidic active pharmaceutical ingredient is selected from salicylates, propionine acid derivatives, acetic acid derivatives, enolic acid derivatives and fenamic acid derivatives.

12. An edible orally disintegrating tablet as claimed in claim 1 , wherein the acidic active pharmaceutical ingredient is ketoprofen.

13. An edible orally disintegrating tablet as claimed in claim 1 , wherein the active ingredient is present in the oral tablets in an amount ranging from about 3 mg to about 75 mg per unit.

14. An edible orally disintegrating tablet as claimed in claim 1 , wherein the anion exchange resin is a strongly basic anion exchange resin.

15. An edible orally disintegrating tablet as claimed in claim 1 , wherein the anion exchange resin is cholestyramine.

16. An edible orally disintegrating tablet as claimed in claim 1 , wherein said tablet comprises at least one emulsifier selected from castor oil derivatives, cetyl and palmityl alcohol, ethanol, hydrogenated vegetable oils, polyvinyl alcohol, simethicone, sorbitan ester, glyceryl monostearate, polyoxyethylene alkyl ethers, polyoxyethylene stearates, poloxamer, polyethylene sorbitan fatty acid esters and mixtures thereof.

17. An edible orally disintegrating tablet as claimed in claim 1 , wherein said tablet further comprises at least one ancillary component selected from bioadhesives for mucosal binding, buffering agents for additional pH control, coloring agents, stabilizing agents, antioxidants, fillers, permeation enhancers, plasticizers and microbial preservatives.

18. An edible orally disintegrating tablet as claimed in claim 1 , wherein said tablet comprises ketoprofen as the active pharmaceutical ingredient, cholestyramine as the anion exchange resin, an alkaline agent, and secondary taste masking agents comprising a taste receptor blocking agent, a cooling sensation agent, at least two sweeteners and one or more flavoring agents.

19. An edible orally disintegrating tablet as claimed in claim 1 , wherein said tablet comprises ketoprofen as the active pharmaceutical ingredient in an amount ranging from about 10 to 50 wt % based on the weight of the tablet; at least one anion exchange resin in an amount ranging from about 12 to 50 wt % based on the weight of the tablet; an effective amount of an alkaline agent, a taste receptor blocking agent in an amount ranging from about 0.17 to 6.5 wt % based on the weight of the tablet; a cooling sensation agent in an amount ranging from about 0.7 to 3.0 wt % based on the weight of the tablet; a sweetener composition comprising at least two sweeteners in amount ranging from about 0.25 to 3.0 wt % based on the weight of the tablet; and one or more flavouring agents in an amount ranging from about 0.3 to 4.5 wt % based on the weight of the tablet.

20. An edible orally disintegrating tablet as claimed in claim 1 , wherein said acidic active pharmaceutical ingredient is uniformly mixed within said tablet.

21. An edible orally disintegrating tablet as claimed is claim 1 , wherein said tablet comprises a first edible alkaline agent and a second edible alkaline agent, said second alkaline agent imparting pH stabilization.

Assignees

• Lts Lohmann Therapie Systeme Ag

Inventors

• Li Michael
• Krumme Markus

Classifications

• A61K31/192 Primary

  having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid  {(cannabinoids A61K31/658)} · CPC title

• B29C39/36

  Removing moulded articles · CPC title

• A61K47/10

  Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers · CPC title

• B29B2013/005

  Degassing undesirable residual components, e.g. gases, unreacted monomers, from material to be moulded · CPC title

• B29C39/02

  for making articles of definite length, i.e. discrete articles · CPC title