Stabilized Granules Containing Glyceryl Trinitrate

Abstract

Solid pharmaceutical preparation with the active substance glyceryl trinitrate for oromucosal or oral administration characterized in that it contains between 0.05 and 2 weight % glyceryl trinitrate, at least one carrier material, and at least one substance that reduces the volatility of the GTN, whereby this substance is a non-volatile ester stabilizer.

1 - 20 . (canceled) 
     
     
         21 . A solid pharmaceutical preparation for oromucosal or oral administration comprising:
 0.05-2% by weight active substance glyceryl trinitrate (GTN;   at least one diluent;   one carrier material; and   at least one substance that reduces the volatility of GTN, whereby the at least one substance is a non-volatile ester stabilizer having a melting point not higher than 60° C.   
     
     
         22 . The pharmaceutical preparation of  claim 21 , wherein the GTN content is 0.1-1% by weight. 
     
     
         23 . The pharmaceutical preparation of  claim 21 , wherein the non-volatile ester is solid or semi-solid at a temperature of 20° C. 
     
     
         24 . The pharmaceutical preparation of  claim 21 , wherein the non-volatile ester stabilizer is selected from the group consisting of: mono- and diglycerides, polyethoxylated glycerides, esters of lactic acid, D-alpha tocopheryl polyethylene glycol 1000 succinate and solid triglycerides, and mixtures thereof. 
     
     
         25 . The pharmaceutical preparation of  claim 21 , wherein the non-volatile ester stabilizer is 0.2-10% by weight. 
     
     
         26 . The pharmaceutical preparation of  claim 21 , wherein the GTN, diluent and stabilizer form a homogeneous solution. 
     
     
         27 . The pharmaceutical preparation of  claim 21 , wherein the mass ratio of the non-volatile ester stabilizer to GTN is between 2 and 40. 
     
     
         28 . The pharmaceutical preparation of  claim 21 , wherein the mass ratio of diluent to the non-volatile ester stabilizer is between 1 and 9.5. 
     
     
         29 . The pharmaceutical preparation of  claim 21 , wherein the carrier material is selected from the group consisting of: magnesium aluminometasilicate, dibasic calcium phosphate, isomalt and mixtures thereof. 
     
     
         30 . The pharmaceutical preparation of  claim 21  further comprising at least one excipient suitable for sublingual administration, wherein the at least one excipient is selected from the group consisting of: water-soluble mono-, di-, and polysaccharides, as well as their respective alcohols. 
     
     
         31 . The pharmaceutical preparation of  claim 30 , wherein the at least one excipient suitable for sublingual administration is selected from the group consisting of: fructose, glucose, isomalt, lactose, maltose, maltitol, mannitol, sorbitol, sucrose, trehalose, and xylitol and mixtures thereof. 
     
     
         32 . The pharmaceutical preparation of  claim 31 , wherein the at least one excipient suitable for sublingual administration comprising at a minimum xylitol and/or isomalt, and wherein their concentration is 20-95% by weight. 
     
     
         33 . The pharmaceutical preparation of  claim 31 , wherein the at least one excipient suitable for sublingual administration is isomalt, and wherein its concentration is 70-95% by weight. 
     
     
         34 . The pharmaceutical preparation of  claim 21 , wherein the preparation is in the form of a free-flowing powder or free-flowing granules. 
     
     
         35 . The pharmaceutical preparation of  claim 34 , wherein the preparation is packaged as a single dose in the form of a stick pack or sachet. 
     
     
         36 . The pharmaceutical preparation of  claim 21 , wherein the preparation further comprises at least 0.01-3.0% by weight of a flavoring agent. 
     
     
         37 . A solid pharmaceutical preparation for oromucosal or oral administration comprising an absorbate comprising 0.05-2% by weight GTN and a non-volatile ester stabilizer on a carrier material. 
     
     
         38 . A method for the manufacture of a solid pharmaceutical preparation for oromucosal or oral administration comprising 0.05-2% by weight active substance glyceryl trinitrate (GTN), the method comprising the steps of:
 a) preparing a GTN solution comprising phlegmatized GTN and at least one non-volatile ester stabilizer,   b) preparing a carrier material,   c) adding the GTN solution to the carrier material,   d) optionally adding further excipients, and   e) mixing until the active substance has been homogeneously distributed, optionally followed by a drying step.   
     
     
         39 . The method of  claim 38 , wherein the carrier material is selected from the group consisting of: magnesium aluminometasilicate, dibasic calcium phosphate, fructose, glucose, isomalt, lactose, maltose, maltitol, mannitol, sorbitol, sucrose, trehalose, xylitol and mixtures thereof. 
     
     
         40 . The method of  claim 38 , wherein the at least one non-volatile ester stabilizer having a melting point not higher than 60° C.