Wafer Comprising Steroid Hormones

Abstract

The invention relates to a pharmaceutical composition in the form of a system in film form for transmucosal administration of steroid hormones. An administration system for steroid hormones which dissolves in the mouth and which releases with a high bioavailability is disclosed. The administration system in film form dissolves in the mouth preferably in a period of less than 30 min, and the steroid hormone entering the bloodstream transmucosally from the administration system leads to a rapid rise in the concentration in the blood. It is thus possible to achieve a maximum concentration of this steroid hormone in the blood in a period of less than 60 min after administration.

1 . An administration system in film form for transmucosal administration of a steroid hormone, comprising:
 0.01-50% by weight of a steroid hormone selected from the group consisting of an estrogen, a progesterone, an androgen, and a mixture thereof;   50-99.99% by weight of a carrier material selected from the group consisting of cellulose, cellulose derivatives, poly-N-vinylpyrrolidones, vinylpyrrolidone-vinyl acetate copolymers, starch, starch derivatives, gelatin, gelatin derivatives, and combinations thereof;   wherein the steroid hormone is dissolved in the carrier material; and   wherein the administration system:
 dissolves in the mouth completely in a period of less than 30 minutes; and 
 releases the steroid hormone contained therein on buccal administration with a bioavailability of at least 50%. 
   
     
     
         2 . The administration system as claimed in  claim 1 ;
 wherein the carrier material is methylcellulose, ethylcellulose, hydroxypropylcellulose, hydroxyethylcellulose, hydroxypropylmethylcellulose (HPMC), or a combination thereof.   
     
     
         3 . The administration system as claimed in  claim 2 ;
 wherein the carrier material is hydroxypropylmethylcellulose (HPMC).   
     
     
         4 . The administration system as claimed in  claim 1 , further comprising:
 liquid excipients which are able to dissolve the steroid hormone and to form a second phase in the carrier material.   
     
     
         5 . The administration system as claimed in  claim 4 ;
 wherein the steroid hormone is present dissolved in the liquid excipient.   
     
     
         6 . The administration system as claimed in  claim 1 ;
 wherein the steroid hormone is present in an amount of from 2 to 15% by weight.   
     
     
         7 . The administration system as claimed in  claim 1 ;
 wherein the administration system has an area of between 1 and 10 cm 2 .   
     
     
         8 . The administration system as claimed in  claim 1 ;
 wherein the administration system has a weight per unit area of between 50 and 250 g/m 2 .   
     
     
         9 . The administration system as claimed in  claim 1 ;
 wherein the administration system has a thickness of between 40 and 130 μm.   
     
     
         10 . The administration system as claimed in  claim 1 ;
 wherein the administration system is mucoadhesive.   
     
     
         11 . The administration system as claimed in  claim 1 ; wherein the administration system dissolves in the mouth completely in a period of less than 15 minutes. 
     
     
         12 . The administration system as claimed in  claim 1 ;
 wherein the androgen is selected from the group consisting of testosterone, dihydrotestosterone, 7α-methyl-19-nortestosterone (MENT), MENT 17-acetate, 7α-methyl-11β-fluoro-19-nortestosterone (eF-MENT), mesterolone, metenolone, nandrolone, oxandrolone, androstenedione, and mixtures thereof.   
     
     
         13 . The administration system as claimed in  claim 1 ;
 wherein the steroid hormone is 7α-methyl-19-nortestosterone (MENT) or 7α-methyl-11β-fluoro-19-nortestosterone (eF-MENT).   
     
     
         14 . The administration system as claimed in  claim 1 , further comprising:
 at least one excipient selected from the group consisting of flavorings, colorants, permeation enhancers, sweeteners, fillers, plasticizers, solubilizers, pH stabilizers, and disintegrants.   
     
     
         15 . The administration system as claimed in  claim 1 ;
 wherein the administration system releases the steroid hormone contained therein on buccal application with a bioavailability of between 70 and 75%.   
     
     
         16 . A method for the treatment of disorders and/or dysfunctions attributable to a steroid hormone deficiency, comprising:
 administering a steroid hormone by the application of the administration system of  claim 1  to a patient in need thereof.   
     
     
         17 . The method as claimed in  claim 16 ;
 wherein the steroid hormone is administered transmucosally.   
     
     
         18 . The method as claimed in  claim 16 ;
 wherein the disorder and/or dysfunction attributable to a steroid hormone deficiency is an androgen deficiency.   
     
     
         19 . The method as claimed in  claim 16 ;
 wherein the steroid hormone reaches a maximum blood concentration in a period of less than 60 min after administration of the medicament.   
     
     
         20 . The method as claimed in  claim 19 ;
 wherein the steroid hormone reaches a maximum blood concentration in a period of less than 30 min after administration of the medicament.   
     
     
         21 . A process for producing an administration system in film form of  claim 1  for transmucosal administration of a steroid hormone, comprising:
 mixing the steroid hormone in the form of a solution in a pharmaceutically acceptable solvent with a water-containing mixture of a carrier material; 
 spreading out the mixture produced by the mixing step as a thin layer; and 
 drying the thin layer by removing the solvent to form a film. 
 
     
     
         22 . The process as claimed in  claim 21 ;
 wherein the resulting film is divided into individual administration systems by perforation, cutting transversely, and/or cutting longitudinally.   
     
     
         23 . A method for the treatment of disorders and/or dysfunctions attributable to a steroid hormone deficiency, comprising:
 a first step of applying the administration system of  claim 1 , which comprises at least one steroid hormone, to the mucosa in the mouth; and   a second step where the at least one steroid hormone penetrates transmucosally into the bloodstream.   
     
     
         24 . The method as claimed in  claim 23 ;
 wherein the steroid hormone penetrates into the bloodstream in a period of less than 30 min after application of the administration system to the mucosa in the mouth.   
     
     
         25 . The administration system as claimed in  claim 1 ;
 wherein the system comprises:
 (1) between 3 and 8% by weight of the steroid hormone; 
 (2) has an area of between 5 and 8 cm 2 ; 
 (3) has a weight per unit area of between 100 to 250 g/m 2 ; and 
 (4) has a thickness of between 50 and 130 μm. 
   
     
     
         26 . The administration system as claimed in  claim 25 ;
 wherein the weight per unit area is between 100 to 150 g/m 2 ; and   wherein the thickness is between 50 and 100 μm.   
     
     
         27 . The administration system as claimed in  claim 1 ;
 wherein the steroid hormone is ethinylestradiol.   
     
     
         28 . The administration system as claimed in  claim 1 ;
 wherein the steroid hormone is selected from the group consisting of drospirenone, dienogest, gestodene, levonorgestrel, cyproterone acetate, and mixtures thereof.   
     
     
         29 . A method for the treatment of a disorder or dysfunction attributable to a steroid hormone deficiency, comprising:
 administering a steroid hormone by the application of the administration system of  claim 1  to a patient in need thereof;   wherein the disorder or dysfunction is selected from the group consisting of androgen deficiency, asthma, arthritis, cancers, diabetes, cardiovascular disorders, gall bladder disorders, and neurological disorders.   
     
     
         30 . The method as claimed in  claim 27 ;
 wherein the disorder or dysfunction is male testosterone deficiency.