Fast acting orally disintegrating film

• US 10,456,378 B2
• Filed: 11/14/2016
• Issued: 10/29/2019
• 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
• Primary Examiner(s): Ricci, Craig D
• Application Number:
  US15/351,368
• Publication Number:
  US 20170056374A1
• Time in Patent Office: 1,079 Days
• Field of Search: None
• 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 about 2 to about 24 mg;

a first hydrophilic film forming polymer comprising hydroxylpropylmethylcellulose (HPMC) in a total amount of from about 15% to about 50% by weight of said film, wherein said first hydrophilic film forming polymer is characterized by having a molecular weight of about 5000Da to about 50000Da and viscosity of about 3 cps or about 6 cps;

a second hydrophilic film forming polymer comprising HPMC characterized by having a molecular weight between about 50000Da to about 60000Da and viscosity of about 15 cps, and said first hydrophilic film forming polymer is mixed with said second hydrophilic film forming polymer in a ratio from about 0.3;

1 to about 7;

1; and

a water soluble excipient comprising polyethylene glycol (PEG) in an amount of about 10% to about 30% by weight of said film;

wherein the fast acting orally disintegrating film disintegrates within about 30 seconds in about 20 cc of water at about 37 degrees Celsius and lightly shaken.

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 from about 0.5:

1 to about 7;

1.

3. The fast acting orally disintegrating film of claim 1 comprising said first hydrophilic film forming polymer in a total amount of from about 20% to about 50% by weight of said film.

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

5. 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 comprising ondansetron or pharmaceutical acceptable salt thereof in an amount of about 4 to about 8 mg;

a first hydrophilic film forming polymer comprising hydroxylpropylmethylcellulose (HPMC) in an amount of from about 15% to about 50% by weight of the film, said first hydrophilic film forming polymer is characterized by having a molecular weight of about 5000 Da to about 50000 Da and viscosity of about 3 cps or about 6 cps;

a second hydrophilic film forming polymer comprising HPMC characterized by having a molecular weight of between about 50000 Da to about 60000 Da and viscosity of about 15 cps, wherein said first hydrophilic film forming polymer is mixed with said second film forming polymer in a ratio from about 0.3;

1 to about 7;

1; and

a water soluble excipient comprising polyethylene glycol (PEG) in an amount of about 10% to about 30% by weight of the film;

wherein the fast acting orally disintegrating film disintegrates within about 30 seconds in about 20 cc of water at about 37 degrees Celsius and lightly shaken.

6. The orally administered film of claim 5 comprising a mixture of said first hydrophilic film forming polymers to said second hydrophilic film forming polymers in a ratio from about 0.5:

1 to about 7;

1.

7. The orally administered film of claim 5 comprising said first hydrophilic film forming polymer in an amount of from about 20% to about 50% by weight of said film.

8. The orally administered film of claim 5 further comprising one or more flavoring agent, sweetening agent and/or coloring agent.