Oral thin film

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.

1 . 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. 
     
     
         2 . The oral thin film according to  claim 1 , wherein the at least one pharmaceutically active agent comprises ketamine, preferably (S)-ketamine or a pharmaceutically acceptable salt thereof. 
     
     
         3 . The oral thin film according to  claim 1 , wherein the at least one pharmaceutically active agent is provided in the matrix layer in an amount of 45 to 70 wt. %, preferably of 50 to 65 wt. %, in relation to the total weight of the matrix layer. 
     
     
         4 . The oral thin film according to  claim 1 , wherein the at least one polyvinyl alcohol comprises a polyvinyl alcohol with a mean molecular weight of approximately 25,000 to approximately 250,000 g/mol. 
     
     
         5 . The oral thin film according to  claim 1 , wherein the at least one polyvinyl alcohol comprises a polyvinyl alcohol with a mean molecular weight of approximately 25,000 to approximately g/mol and/or a polyvinyl alcohol with a mean molecular weight of approximately 200,000 to 210,000 g/mol. 
     
     
         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. 
     
     
         7 . 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. 
     
     
         8 . 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, preferably of approximately 45,000 g/mol. 
     
     
         9 . The oral thin film according to  claim 1 , wherein the at least one polyvinyl alcohol is provided in the matrix layer in an amount of 5 to 40 wt. %, preferably of 5 to 10 wt. %, in relation to the total weight of the matrix layer. 
     
     
         10 . The oral thin film according to  claim 1 , wherein the at least one polyvinyl alcohol-polyethylene glycol graft copolymer is provided in the matrix layer in an amount of 15 to 45 wt. %, preferably of 17 to 40 wt. %, in relation to the total weight of the matrix layer. 
     
     
         11 . 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. 
     
     
         12 . The oral thin film according  claim 1 , wherein the area density of the oral thin film is approximately 50 to 300 g/m 2 . 
     
     
         13 . The oral thin film according to  claim 1 , wherein the at least one pharmaceutically active agent comprises ketamine as a free base in a total amount of 25 to 150 mg, preferably of approximately 50 to 150 mg. 
     
     
         14 . The oral thin film according to  claim 1 , wherein at least 40% or at least 50% of the at least one pharmaceutically active agent are released within the first minute following application, and/or wherein at least 75%, at least 80% or at least 85% of the at least one pharmaceutically active agent are released within the first two minutes following application. 
     
     
         15 . The oral thin film according to  claim 1 , wherein the puncture strength is at least 0.15 N/mm 2 , preferably at least 0.18 N/mm 2  and especially preferably at least 0.20 N/mm 2 , with an areal density of 150 to 250 g/m 2 , preferably of 180 to 220 g/m 2 . 
     
     
         16 . 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, preferably of 205,000 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, preferably of approximately 45,000 g/mol. 
     
     
         17 . 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. 
     
     
         18 . 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. 
     
     
         19 . 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. 
     
     
         20 . A method for producing an oral thin film according to  claim 1 , comprising the steps of:
 producing a solution, dispersion or melt comprising the at least one pharmaceutically active agent, the at least one polyvinyl alcohol and the at least one polyvinyl alcohol-polyethylene glycol graft copolymer;   a1) optionally foaming the solution, dispersion or melt from step a) by introducing a gas or gas mixture, by chemical gas generation or by expansion of a dissolved gas,   the solution, dispersion or melt from step a) or the optionally foamed solution, dispersion or melt from step a1.   
     
     
         21 . (canceled)