# US 2014/0155483 A1 · Edible Oral Strip or Wafer Dosage Form Containing Ion Exchange Resin for Taste Masking

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- Number: US 2014/0155483 A1
- Document ID: US20140155483A1
- Status: Published application
- Kind: A1
- Application number: 14/123,490
- Filed: 2012-05-30
- Published: 2014-06-05
- Earliest claimed: 2011-06-08
- Assignees: LTS Lohmann Therapie-Systeme AG
- Inventors: Michael Hsin Chwen Li; Markus Krumme
- Web page: https://patentgrep.com/patent/US20140155483A1

## CPC

- A61K 36/47: Euphorbiaceae (Spurge family), e.g. Ricinus (castorbean)
- A23L 27/88: {Taste or flavour enhancing agents}
- A61K 9/006: {Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays}
- A61K 31/192: having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid {(cannabinoids A61K31/658)}
- A61K 47/10: Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
- A61K 47/186: {Quaternary ammonium compounds, e.g. benzalkonium chloride or cetrimide}
- A61K 47/26: Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
- A61K 47/32: Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers {, poly(meth)acrylates, or polyvinyl pyrrolidone}
- A61K 47/36: Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K 47/38: Cellulose; Derivatives thereof
- A61K 47/46: Ingredients of undetermined constitution or reaction products thereof, e.g. skin, bone, milk, cotton fibre, eggshell, oxgall or plant extracts
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- B29B 7/88: Adding charges {, i.e. additives}
- B29B 13/00: Conditioning or physical treatment of the material to be shaped (chemical aspects C08J3/00 {; heating, cooling or curing during shaping B29C35/00; thermal after-treatment B29C71/02})
- B29C 39/02: for making articles of definite length, i.e. discrete articles
- B29C 39/36: Removing moulded articles
- B29C 39/38: Heating or cooling
- B29C 41/003: {characterised by the choice of material}
- B29C 69/001: {a shaping technique combined with cutting, e.g. in parts or slices combined with rearranging and joining the cut parts (for reinforced material B29C70/545; B29C49/4278, B29C51/268 take precedence)}
- A23V 2002/00: Food compositions, function of food ingredients or processes for food or foodstuffs
- B29B 2013/005: {Degassing undesirable residual components, e.g. gases, unreacted monomers, from material to be moulded}
- B29K 2105/0035: {Medical or pharmaceutical agents}
- B29L 2007/007: {Narrow strips, e.g. ribbons, tapes, bands (belts B29L2029/00; tapes as carrier of sound or information B29L2017/008)}
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A23L: FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF (preservation thereof A23B)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- B29B: PREPARATION OR PRETREATMENT OF THE MATERIAL TO BE SHAPED; MAKING GRANULES OR PREFORMS; RECOVERY OF PLASTICS OR OTHER CONSTITUENTS OF WASTE MATERIAL CONTAINING PLASTICS
- B29C: SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING (making preforms B29B11/00; making laminated products by combining previously unconnected layers which become one product whose layers will remain together B32B37/00 - B32B41/00)
- A23V: INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- B29K: INDEXING SCHEME ASSOCIATED WITH SUBCLASSES B29B, B29C OR B29D, RELATING TO MOULDING MATERIALS OR TO MATERIALS FOR {MOULDS, } REINFORCEMENTS, FILLERS OR PREFORMED PARTS, e.g. INSERTS
- B29L: INDEXING SCHEME ASSOCIATED WITH SUBCLASS B29C, RELATING TO PARTICULAR ARTICLES

## Abstract

An edible oral film strip 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 oral film strip 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.

## Claims

### Claim 1

An edible oral film strip comprising
at least one water dispersible or water disintegrable film forming polymer,
an acidic active pharmaceutical ingredient and
at least one anion exchange resin as a primary taste masking agent.

### Claim 2 (depends on 1)

An edible oral film strip as claimed in claim 1, wherein said strip further comprises an edible alkaline agent.

### Claim 3 (depends on 2)

An edible oral film strip as claimed in claim 2, wherein said alkaline agent is selected from hydroxides, edible bicarbonates, edible carbonates, basic amino acids, buffers and mixtures thereof.

### Claim 4 (depends on 1)

An edible oral film strip as claimed in claim 1, wherein said strip further comprises one or more secondary taste masking agents.

### Claim 5 (depends on 4)

An edible oral film strip as claimed in claim 4, 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).

### Claim 6 (depends on 5)

An edible oral film strip as claimed in claim 5, 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.

### Claim 7 (depends on 4)

An edible oral film strip as claimed in claim 4, 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.

### Claim 8 (depends on 4)

An edible oral film strip 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 frutti, apple, coffee, plum, watermelon, nuts, green tea, grapefruit, banana, butter, and chamomile.

### Claim 9 (depends on 4)

An edible oral film strip as claimed in claim 4, 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.

### Claim 10 (depends on 4)

An edible oral film strip as claimed in claim 4, wherein the secondary taste masking agent comprises PEG-40 Hydrogenated Castor Oil as a taste receptor blocker.

### Claim 11 (depends on 1)

An edible oral film strip 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.

### Claim 12 (depends on 1)

An edible oral film strip as claimed in claim 1, wherein the acidic active pharmaceutical ingredient is ketoprofen.

### Claim 13 (depends on 1)

An edible oral film strip as claimed in claim 1, wherein the active ingredient is present in the oral film strips in an amount ranging from about 3 mg to about 75 mg per unit.

### Claim 14 (depends on 1)

An edible oral film strip as claimed in claim 1, wherein the anion exchange resin is a strongly basic anion exchange resin.

### Claim 15 (depends on 1)

An edible oral dim strip as claimed in claim 1, wherein the anion exchange resin is cholestyramine.

### Claim 16 (depends on 1)

An edible oral film strip as claimed in claim 1, wherein the film forming polymer is one of more of cellulose, cellulose derivatives, synthetic or natural gums, methacrylic acid polymers, methacrylic acid copolymers, acrylic acid polymers, acrylic acid copolymers, polyacrylamides, polyalkylene oxides, polyalkylene glycols, carrageanan, pullunan, locust bean gums, bean starches, polyvinyl pyrrolidone, polyvinyl alcohol alginic acid, salts of alginic acid, carboxyvinyl polymers, pectin, pectin derivatives, xanthan gum, xanthan gum derivatives, pea starch and starch derivatives and mixtures thereof.

### Claim 17 (depends on 1)

An edible oral film strip as claimed in claim 1, wherein the film forming polymer is a cellulose derivative selected from methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, carboxymethyl cellulose, sodium carboxymethyl cellulose, and mixtures thereof.

### Claim 18 (depends on 1)

An edible oral film strip as claimed in claim 1, wherein the film forming polymer is a mixture of sodium carboxymethylcellulose or methylcellulose and hydroxypropylmethylcellulose.

### Claim 19 (depends on 1)

An edible oral film strip as claimed in claim 1, wherein the oral film strip 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.

### Claim 20 (depends on 1)

An edible oral film strip as claimed in claim 1, wherein the oral film strip 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.

### Claim 21 (depends on 1)

An edible oral film strip as claimed in claim 1, wherein said oral film strip 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.

### Claim 22 (depends on 1)

An edible oral film strip as claimed in claim 1, wherein said oral film strip comprises
Ketoprofen as active pharmaceutical ingredient in an amount ranging from about 10 to 50 wt % based on the weight of the dry oral film strip;
at least one anion exchange resin in an amount ranging from about 12 to 50 wt % based on the weight of the dry oral film strip;
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 dry oral film strip;
a cooling sensation agent in an amount ranging from about 0.7 to 3.0 wt % based on the weight of the dry oral film strip;
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 dry oral film strip; and
one or more flavouring agents in an amount ranging from about 0.3 to 4.5 wt % based on the weight of the dry oral film strip.

### Claim 23 (depends on 1)

A method of preparing an edible oral film strip as claimed in claim 1, comprising
dissolving or suspending a clinically effective amount of an acidic active pharmaceutical ingredient into a pharmalogically approved solvent to form an active-ingredient solution;
optionally adjusting the pH of the active-ingredient solution to a pH of between 5.0 and 10.0;
introducing at least one anion ion exchange resin into the optionally pH adjusted active ingredient solution;
admixing the active-ingredient/anion exchange resin solution with one or more water-soluble or water-miscible polymers to produce a film-forming composition;
optionally incorporating one or more excipients selected from cooling agents, emulsifiers, flavouring agents, sweeteners, taste receptor blockers or ancillary excipients,
optionally sonicating and/or vacuuming the film-forming composition to remove entrapped air;
coating, extruding or casting the optionally deaereated film forming composition onto a casting substrate to form a wet film,
drying the coated, extruded or cast wet film;
removing the dried film from the casting substrate; and
cutting the dried film into individual oral film strips.

### Claim 24

A method of administering an edible oral film strip comprising applying an edible oral film strip dosage to the oral cavity of a patient, optionally via a mucoadhesive, and allowing the dosage to dissolve for subsequent absorption in the GI tract of the patient.

### Claim 25

An edible oral film strip comprising
at least one water dispersible or water disintegrable film forming polymer,
a basic active pharmaceutical ingredient,
at least one cation exchange resin as a primary taste masking agent,
an optional edible acidic agent,
and one or more optional secondary taste masking agents.