Production Of Pharmaceutical Protective Coatings With Good Resistance In A Neutral Environment

Abstract

Pharmaceutical coatings obtained from coating compositions based on film-forming copolymers of N,N-diethylaminoethyl methacrylate (DEAEMA) and methyl methacrylate (MMA) comprising a weight ratio of DEAEMA:MMA in the range of 35:65 to 55:45, where the copolymers are present partially neutralized with C 3 -C 10 -dicarboxylic acids.

1 . A pharmaceutical coating obtained from a film-forming coating composition based on a copolymer of N,N-diethylaminoethyl methacrylate (DEAEMA) and methyl methacrylate (MMA) comprising a weight ratio of DEAEMA:MMA in the range of 35:65 to 55:45, where the copolymer is partially neutralized with a C 3 -C 10 -dicarboxylic acid. 
     
     
         2 . The coating of  claim 1 , wherein the copolymer is partially neutralized with an unbranched C 3 -C 10 -dicarboxylic acid. 
     
     
         3 . The coating of  claim 1 , wherein the dicarboxylic acid comprises fumaric acid. 
     
     
         4 . The coating of  claim 1 , wherein the dicarboxylic acid comprises an alkanedicarboxylic acid. 
     
     
         5 . The coating of  claim 1 , wherein the dicarboxylic acid is selected from the group consisting of malonic acid, succinic acid, glutaric acid, adipic acid or sebacic acid, malic acid (2-hydroxysuccinic acid) and tartaric acid (2,3-dihydroxysuccinic acid). 
     
     
         6 . The coating of  claim 1 , wherein the copolymer is partially neutralized to 2 to 15 mol %. 
     
     
         7 . The coating of  claim 6 , wherein the copolymer is partially neutralized to 4 to 10 mol %. 
     
     
         8 . The coating of  claim 1 , the dicarboxylic acid comprising dicarboxylic acids which have a first pK a  value of greater than 2 and a second pK a  value of greater than 4. 
     
     
         9 . The coating of  claim 5 , the dicarboxylic acid comprising adipic acid. 
     
     
         10 . A dosage form comprising a pharmaceutical active ingredient and the coating composition according to  claim 1 . 
     
     
         11 . The dosage form of  claim 10 , wherein the coating composition is applied in an amount in the range of 1 to 20 mg/cm 2    
     
     
         12 . The dosage form of  claim 10 , wherein upon application of the coating composition in an amount of 4 mg/cm 2 , having a resistance to release of the pharmaceutical active ingredient in an aqueous environment at pH 6.8 of at least 80% after 30 min. 
     
     
         13 . The dosage form of  claim 10 , wherein the coating composition is obtained by applying an aqueous coating which is prepared by redispersing the coating composition from a powder form. 
     
     
         14 . A method for producing a film-forming coating composition for a dosage form comprising at least one pharmaceutical active ingredient and having a resistance to premature release of the active ingredient, the method comprising
 forming the coating composition comprising a copolymer of N,N-diethylaminoethyl methacrylate (DEAEMA) and methyl methacrylate (MMA) comprising a weight ratio of DEAEMA:MMA in the range of 35:65 to 55:45, and   partially neutralizing the copolymers in the coating composition with a C 3 -C 10 -dicarboxylic acid.   
     
     
         15 . The method of  claim 14 , wherein the partially neutralizing step occurs with the dicarboxylic acid in an aqueous dispersion. 
     
     
         16 . The method of  claim 14 , wherein the copolymer is partially neutralized in powder form. 
     
     
         17 . The method of  claim 14 , wherein the copolymer is partially neutralized to 2 to 15 mol %. 
     
     
         18 . The method of  claim 17 , wherein the copolymer is partially neutralized to 4 to 10 mol %. 
     
     
         19 . The method of  claim 18 , wherein the copolymer is partially neutralized with an unbranched C 3 -C 10 -dicarboxylic acid. 
     
     
         20 . The method of  claim 14 , wherein the dicarboxylic acid comprises an alkane dicarboxylic acid. 
     
     
         21 . The method of  claim 20 , wherein the dicarboxylic acid is selected from the group consisting of malonic acid, succinic acid, glutaric acid, adipic acid or sebacic acid, malic acid (2-hydroxysuccinic acid) and tartaric acid (2,3-dihydroxysuccinic acid). 
     
     
         22 . The method of  claim 21 , wherein the dicarboxylic acid comprises adipic acid. 
     
     
         23 . The method of  claim 14 , wherein the dicarboxylic acid comprises fumaric acid. 
     
     
         24 . The method of  claim 14  further comprising redispersing the coating composition in water prior to application to a dosage form. 
     
     
         25 . A method of making a dosage form comprising using the coating composition of  claim 1  and applying it to an active ingredient, the coating composition providing protection against premature release of the active ingredient in an aqueous environment at pH 6.8.