Transmucosal Administration System for a Pharmaceutical Drug

Abstract

The invention generally relates to transmucosal administration systems for administering quinones, benzoquinones, and especially 1,4-benzoquinones, via the oromucosal route. The present invention more specifically relates to methods of treatment for Duchenne Muscular Dystrophy that includes administering to a patient a dose in the form of one or more transmucosal administration systems.

That which is claimed: 
     
         1 . A method of treatment for Duchenne Muscular Dystrophy (“DMD”) comprising administering to a patient a dose consisting of one or more transmucosal administration systems consisting of a polymer-based film by attaching said film in the oral cavity of a patient with subsequent release of a pharmaceutical active ingredient to the mucosa, the system containing 0.01to 80% by weight of idebenone as active ingredient and
 a carrier material comprising polyalcohol and/or a cellulose derivative, 
 the system is a mucoadhesive wafer which dissolves in the mouth, with the idebenone primarily absorbed through the mucosa, 
 the system exhibits an AUC 0-360 /mg of the active ingredient concentration in the patient's blood that is greater than that exhibited through administering the active ingredient through the oral route on a dose normalized basis. 
 
     
     
         2 . The method of treatment as claimed in  claim 1 , wherein said administering step comprises administering the polymer-based film onto the oral mucosa on or under the tongue in the buccal cavity or any other location in the oral cavity. 
     
     
         3 . The method of treatment as claimed in  claim 1 , wherein said administration system further comprises a second therapeutic agent. 
     
     
         4 . The method of treatment as claimed in  claim 3 , wherein said second therapeutic agent is selected from glucocorticosteroids, deflazacort and any medicament used to treat DMD-associated cardiomyopathy. 
     
     
         5 . The method of treatment as claimed in  claim 4 , wherein said glucocorticosteroid is 6a-methylprednisolone-21 sodium succinate and the medicament used to treat DMD-associated cardiomyopathy is an ACE-inhibitor, beta-blocker, diuretic or HMG-CoA reductase inhibitor. 
     
     
         6 . The method of treatment as claimed in  claim 1 , wherein said active ingredient is either dissolved in the carrier material thereby forming a molecularly dispersed solid solution or is present as a micronized suspension within the carrier material. 
     
     
         7 . The method of treatment as claimed in  claim 2 , wherein a mucoadhesive wafer containing 15 mg of said molecularly dispersed active ingredient exhibits an AUC 0-360 /mg of the active ingredient in the blood that is 4.75 times higher than the AUC 0-360 /mg of said mucoadhesive wafer containing 30 mg of suspended micronized pharmaceutical active ingredient after dose normalization per mg. 
     
     
         8 . The method of treatment as claimed in  claim 1 , wherein the idebenone is administered in a dosage of equal to or less than 60 mg/kg/day. 
     
     
         9 . The method of treatment as claimed in  claim 1 , wherein the idebenone is administered in a dosage ranging from 0.01 mg/kg/day to 20 mg/kg/day. 
     
     
         10 . The method of treatment as claimed in  claim 3 , wherein the idebenone is administered in a dosage ranging from 0.01 mg/kg/day to 10 mg/kg/day. 
     
     
         11 . The method of treatment as claimed in  claim 1 , wherein the film dissolves completely in a period of less than 30 minutes in the mouth. 
     
     
         12 . The method of treatment as claimed in  claim 1 , wherein a maximum concentration of the active ingredient in the blood is reached in a period of less than 240 minutes after application. 
     
     
         13 . The method of treatment as claimed in  claim 11 , wherein a maximum concentration of the active ingredient in the blood is reached at a period of between 5 and 30 min after application. 
     
     
         14 . The method of treatment as claimed in  claim 1 , wherein said wherein the transmucosal administration system comprises optional excipient consisting of one or more of flavorings, colorants, sweeteners, fillers, plasticizers, surface-active substances, solubilizers, liquid excipient, disintegrants, solubility enhancers and absorption enhancers. 
     
     
         15 . The method of treatment as claimed in  claim 1 , wherein the carrier material comprises cellulose, cellulose derivatives, polyvinyl-alcohol, poly-N-vinylpyrrolidones, vinylpyrrolidone-vinyl acetate copolymers, starch, starch derivatives, gelatin, gelatin derivatives, and combinations thereof. 
     
     
         16 . The method of treatment as claimed in  claim 15 , wherein the cellulose derivative is methylcellulose, ethylcellulose, hydroxypropylcellulose, hydroxyethylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose or combinations thereof. 
     
     
         17 . The method of treatment as claimed in  claim 1 , wherein said system comprises
 50% by weight of active ingredient and 40% by weight polyvinyl alcohol and 10% by weight of sodium carboxymethyl-cellulose as carrier material, or   said system comprises 10% by weight of active ingredient and 90% by weight of hydroxypropylmethylcellulose as carrier material.   
     
     
         18 . The method of treatment as claimed in  claim 1 , wherein said patient has swallowing difficulties. 
     
     
         19 . The method of treatment as claimed in  claim 1 , wherein the system has a monolayer or double-layer construction.