Fast Acting Orally Disintegrating Film

• US 20170056374A1
• Filed: 11/14/2016
• Published: 03/02/2017
• Est. Priority Date: 06/24/2014
• Status: Active Grant

• Current Assignee: TAHO Pharmaceuticals Ltd.
• Original Assignee: TAHO Pharmaceuticals Ltd.
• Inventors: Lee, Catherine, Wang, Chien-Chiao
• Granted Patent: US 10,456,378 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 31/4178 not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: 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
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• CPC Class Codes: A61K 47/38 Cellulose; Derivatives thereof
• 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 9/7007 Drug-containing films, membranes or sheets A61K9/0041, A61K9/0043, A61K9/006, A61K9/0063 take precedence
• CPC Class Codes: A61P 1/08 for nausea, cinetosis or vertigo; Antiemetics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

A fast acting orally disintegrating film (ODF) for treatment of various medical conditions including emesis that has a simple formulation, easy to manufacture and has similar pharmacokinetic profile to currently commercially available orally administered drug products is provided. The ODF comprises an active pharmaceutical ingredient such as ondansetron or a pharmaceutical acceptable salt thereof in an amount of 2 to 24 mg, at least one hydrophilic film forming polymer in an amount of at least 8% by weight of the film, wherein the at least one hydrophilic film forming polymer is characterized by having a molecular weight of 5000 to 50000 Da, and a water soluble excipient in an amount of 10 to 30% by weight of the film. The present invention also provides a method for preparing the ODF that remains stable over a period of time under a normal pharmacologically storage condition and a method for treating or preventing various medical conditions such as nausea or vomiting or a treatment method mediated through antagonizing action of 5HT at 5-HT3 receptor by administering the ODF to a patient in need thereof.

Claims

1. A fast acting orally disintegrating film, comprising:

ondansetron or a pharmaceutical acceptable salt thereof in an amount of 2 to 24 mg;

a first hydrophilic film forming polymer in a total amount of at least about 8% by weight of said film, wherein said first hydrophilic film forming polymer is characterized by having a molecular weight of 5000 Da to 50000 Da and viscosity of about 3 cps to about 10 cps;

a second hydrophilic film forming polymer characterized by having a molecular weight of equal or greater than about 50000 Da and viscosity equal or greater than about 15 cps, and said first hydrophilic film forming polymers mixed with said second hydrophilic film forming polymer in a ratio of at least about 0.1;

1; and

a water soluble excipient in an amount of about 10% to about 30% by weight of said film.

2. The fast acting orally disintegrating film of claim 1 comprising a mixture of said first hydrophilic film forming polymer to said second hydrophilic film forming polymer in a ratio of more than about 0.5:

1.

3. The fast acting orally disintegrating film of claim 1 comprising said first hydrophilic film forming polymer in a total amount of more than about 20% by weight of said film.

4. The fast acting orally disintegrating film of claim 1 comprising said first hydrophilic film forming polymer in a total amount of more than about 50% by weight of said film.

5. The fast acting orally disintegrating film of claim 1 comprising said first hydrophilic film forming polymer in a total amount of more than about 65% by weight of said film.

6. The fast acting orally disintegrating film of claim 1, wherein said first hydrophilic film forming polymer comprises at least one member selected from hydroxylpropylmethylcellulose, hydroxypropylcellulose, and povidone.

7. The fast acting orally disintegrating film of claim 1, wherein said first and second hydrophilic film forming polymer comprise at least one member selected from hydroxylpropylmethylcellulose, hydroxypropylcellulose, carboxymethylcellulose, polysaccharide polymer and povidone.

8. The fast acting orally disintegrating film of claim 1 wherein said water soluble excipient comprises polyethylene glycol (PEG).

9. The fast acting orally disintegrating film of claim 1 further comprising one or more flavoring agent, sweetening agent and/or coloring agent.

10. A method for preparing an orally administrable film dosage form, comprising:

dissolving a pharmaceutically acceptable amount of ondansetron, a first film forming polymer in an amount of at least about 8% by weight of said dosage form and a water-soluble excipient in an amount of about 10% to about 30% by weight of said dosage form in water to form a viscous solution with a measured viscosity of about 2000 cps to about 10000 cps;

mixing into the viscous solution a second hydrophilic film forming polymer characterized by having a molecular weight of equal or greater than 50000 Da and viscosity equal to or greater than about 15 cps, wherein said first hydrophilic film forming polymer is mixed with said second hydrophilic film forming polymer in a ratio of at least about 0.1;

1; and

coating a layer of said viscous solution on a casting film and drying in an oven at about 80°

C. over a period of about 20 minutes;

wherein said first hydrophilic film forming polymer is characterized by having a molecular weight of 5000 Da to 50000 Da and viscosity of about 3 cps to about 10 cps.

11. The method of claim 10 further comprising a mixture of said first hydrophilic film forming polymer to said second hydrophilic film forming polymer in a ratio of more than about 0.5:

1.

12. The method of claim 10, wherein said first hydrophilic film forming polymers comprises at least one member selected from hydroxylpropylmethylcellulose, hydroxypropylcellulose and/or povidone.

13. The method of claim 10, wherein said first hydrophilic film forming polymer and said second hydrophilic film forming polymer comprise at least one member selected from hydroxylpropylmethylcellulose, hydroxypropylcellulose, carboxymethylcellulose, polysaccharide polymer and/or povidone.

14. The method of claim 10, wherein said water soluble excipient comprises PEG.

15. The method of claim 10 further comprising the step of dissolving one or more flavoring agent, sweetening agent or coloring agent into said viscous solution.

16. An orally administered film characterized by a pre-drying solution blend with a measured viscosity of about 2000 to about 10000 cps, wherein the pre-drying solution blend comprises:

an active pharmaceutical ingredient or pharmaceutical acceptable salt thereof in an amount of about 4 to 8 mg;

a first hydrophilic film forming polymer in an amount of at least about 8% by weight of the film, said first hydrophilic film forming polymer is characterized by having a molecular weight of 5000 Da to 50000 Da and viscosity of about 3 cps to about 10 cps;

a second hydrophilic film forming polymer characterized by having a molecular weight of equal or greater than 50000 Da and viscosity equal or greater than about 15 cps, wherein said first hydrophilic film forming polymer is mixed with said second film forming polymer in a ratio of at least about 0.1;

1; and

a water soluble excipient in an amount of about 10% to about 30% by weight of the film.

17. The orally administered film of claim 16 comprising a mixture of said first hydrophilic film forming polymers to said second hydrophilic film forming polymers in a ratio of more than about 0.5:

1.

18. The orally administered film of claim 16 comprising said first hydrophilic film forming polymer in an amount of more than about 20% by weight of said film.

19. The orally administered film of claim 16 comprising said first hydrophilic film forming polymer in an amount of more than about 50% by weight of said film.

20. The orally administered film of claim 16 comprising said first hydrophilic film forming polymer in an amount of more than about 65% by weight of said film.

21. The orally administered film of claim 16, wherein said first hydrophilic film forming polymer comprises at least one member selected from hydroxylpropylmethylcellulose, hydroxypropylcellulose, and povidone.

22. The orally administered film of claim 16, wherein said first hydrophilic film forming polymer and said second hydrophilic film forming polymer comprise at least one member selected from hydroxylpropylmethylcellulose, hydroxypropylcellulose, carboxymethylcellulose, polysaccharide polymer and/or povidone.

23. The orally administered film of claim 16 wherein said water soluble excipient comprises PEG.

24. The orally administered film of claim 16 further comprising one or more flavoring agent, sweetening agent and/or coloring agent.

25. The orally administered film of claim 16 wherein said active pharmaceutical ingredient is a member selected from ondansetron, lidocaine, olanzapine, galantamine, rizatriptan, methylphenidate or gransetron.