Oral thin film of polyvinyl alcohol and polyvinyl alcohol-polyethylene glycol graft copolymer

Patent metadata

Field	Value
Publication number	US-11992561-B2
Application number	US-202217900616-A
Country	US
Kind code	B2
Filing date	Aug 31, 2022
Priority date	Nov 9, 2020
Publication date	May 28, 2024
Grant date	May 28, 2024

Abstract

Described is an oral thin film comprising at least one matrix layer, wherein the at least one matrix layer comprises at least one pharmaceutically active agent, at least one polyvinyl alcohol and at least one polyvinyl alcohol-polyethylene glycol graft copolymer, a method for producing same, and use thereof as a medicament.

First claim

The invention claimed is:

1. An oral thin film comprising at least one matrix layer, wherein the at least one matrix layer comprises ketamine in an amount of 45 to 70 wt. %, in relation to the total weight of the matrix layer, at least one polyvinyl alcohol with a mean molecular weight of 200,000 to 210,000 g/mol, in an amount of 5 to 40 wt. % in relation to the total weight of the matrix layer, and at least one polyvinyl alcohol-polyethylene glycol graft copolymer in an amount of 15 to 45 wt. % in relation to the total weight of the matrix layer.

2. The oral thin film according to claim 1 , wherein ketamine comprises a pharmaceutic ally acceptable salt of ketamine.

3. The oral thin film according to claim 1 , wherein the matrix layer further includes at least one polyvinyl alcohol with a mean molecular weight of approximately 25,000 to approximately 35,000 g/mol.

4. The oral thin film according to claim 1 , wherein the at least one polyvinyl alcohol-polyethylene glycol graft copolymer has a polyethylene glycol main chain onto which there are grafted polyvinyl alcohol units.

5. The oral thin film according to claim 1 , wherein the at least one polyvinyl alcohol-polyethylene glycol graft copolymer has a polyethylene glycol main chain onto which there are grafted polyvinyl alcohol units, wherein the molar ratio of polyethylene glycol to polyvinyl alcohol is 1:3.

6. The oral thin film according to claim 1 , wherein the at least one polyvinyl alcohol-polyethylene glycol graft copolymer has a polyethylene glycol main chain onto which there are grafted polyvinyl alcohol units, wherein the polyvinyl alcohol-polyethylene glycol graft copolymer has a mean molecular weight in the range of 40,000 to 50,000 g/mol.

7. The oral thin film according to claim 1 , wherein the oral thin film further comprises at least one auxiliary substance selected from the group comprising colouring agents, flavourings, sweeteners, plasticisers, taste-masking agents, emulsifiers, enhancers, pH regulators, humectants, preservatives and/or antioxidants.

8. The oral thin film according to claim 1 , wherein the area density of the oral thin film is approximately 50 to 300 g/m.

9. The oral thin film according to claim 1 , wherein the ketamine comprises ketamine as a free base in a total amount of 25 to 150 mg.

10. The oral thin film according to claim 1 , wherein at least 40% of the ketamine is released within the first minute following application, and/or wherein at least 75% of the ketamine is released within the first two minutes following application.

11. The oral thin film according to claim 1 , wherein the puncture strength is at least 0.15 N/mm with an areal density of 150 to 250 g/m.

12. The oral thin film according to claim 1 , wherein the matrix layer comprises 60 wt. % of (S)-ketamine HCl, 10 wt. % of a polyvinyl alcohol with a mean molecular weight of approximately 200,000 to 210,000 g/mol, and 20.1 wt. % of a polyvinyl alcohol-polyethylene glycol graft copolymer, wherein the polyvinyl alcohol-polyethylene glycol graft copolymer has a polyethylene glycol main chain onto which there are grafted polyvinyl alcohol units, and wherein the polyvinyl alcohol-polyethylene glycol graft copolymer has a mean molecular weight in the range of 40,000 to 50,000 g/mol.

13. The oral thin film according to claim 1 , wherein the maximum plasma concentration of (S)-ketamine following administration of a dose of 50 mg (S)-ketamine lies at 50 to 200 ng/mL, or wherein the maximum plasma concentration of (S)-ketamine following administration of a dose of 100 mg (S)-ketamine lies at 100 to 200 ng/mL.

14. The oral thin film according to claim 1 , wherein the maximum plasma concentration of the ketamine metabolite (S)-norketamine following administration of a dose of 50 mg (S)-ketamine lies at 200 to 400 ng/mL, or wherein the maximum plasma concentration of the ketamine metabolite (S)-norketamine following administration of a dose of 100 mg (S)-ketamine lies at 300 to 500 ng/mL.

15. The oral thin film according to claim 1 , wherein the maximum plasma concentration of the ketamine metabolite (S)-hydroxynorketamine following administration of a dose of 50 mg (S)-ketamine lies at 50 to 150 ng/mL, or wherein the maximum plasma concentration of the ketamine metabolite (S)-hydroxynorketamine following administration of a dose of 100 mg (S)-ketamine lies at 100 to 250 ng/mL.

Assignees

• Lts Lohmann Therapie Systeme Ag

Inventors

• Müller Markus
• Ficker Mario
• Linn Michael
• Hammes Florian

Classifications

• A61K9/7007 Primary

  Drug-containing films, membranes or sheets (A61K9/0041, A61K9/0043, A61K9/006, A61K9/0063 take precedence) · CPC title

• A61K9/006 Primary

  Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays · CPC title

• A61K31/135

  having aromatic rings {, e.g. ketamine, nortriptyline (methadone A61K31/137)} · CPC title

• A61K47/10

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

• A61K47/32

  Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers {, poly(meth)acrylates, or polyvinyl pyrrolidone} · CPC title