Delayed release rasagiline formulation

Abstract

Disclosed are formulations which are designed to delay release of rasagiline while maintaining specific pharmacokinetic properties.

1 . A stable oral dosage form comprising a core having a production process-resulting form of rasagiline and at least one pharmaceutically acceptable excipient; and an acid resistant pharmaceutically acceptable coating, the production process comprising
 a) preparing the core by admixing rasagiline base, citric acid and/or malic acid, and a pharmaceutically acceptable excipient; and   b) coating the core with the acid resistant pharmaceutically acceptable coating.   
     
     
         2 . The dosage form of  claim 1 , wherein the rasagiline base is crystalline rasagiline base. 
     
     
         3 . The dosage form of  claim 1 , wherein the content of rasagiline is 0.5 mg. 
     
     
         4 . The dosage form of  claim 1 , wherein the content of rasagiline is 1.0 mg. 
     
     
         5 . The dosage form of  claim 1 , wherein step a) comprises preparing a wet granulate of the rasagiline base, citric acid and/or malic acid, and a pharmaceutically acceptable excipient. 
     
     
         6 . The dosage form of  claim 5 , wherein step a) further comprises:
 i) drying the wet granulate to form a dry granulate,   ii) milling the dry granulate to form particles, and   iii) admixing the particles with at least one lubricant.   
     
     
         7 . The dosage form of  claim 6 , wherein in step iii) the lubricant is talc or stearic acid, or a combination thereof. 
     
     
         8 . The dosage form of  claim 6 , wherein in step i) the wet granulate is dried in a fluid bed dryer under inlet air temperature of 40° C. to 50° C., and under outlet air temperature of not greater than 37° C. 
     
     
         9 . The dosage form of  claim 8 , wherein in step i) the inlet air temperature is 45° C. 
     
     
         10 . The dosage form of  claim 6 , wherein in step ii) the dry granulate is milled through an oscillating granulator. 
     
     
         11 . The dosage form of  claim 1 , wherein step a) further comprises a step of forming the core by compression. 
     
     
         12 . The dosage form of  claim 11 , wherein the core is a tablet. 
     
     
         13 . The dosage form of  claim 1 , wherein in step a) the core is prepared by admixing rasagiline base, citric acid, and a pharmaceutically acceptable excipient. 
     
     
         14 . The dosage form of  claim 1 , wherein in step a) the core is prepared by admixing rasagiline base, malic acid, and a pharmaceutically acceptable excipient. 
     
     
         15 . The dosage form of  claim 1 , wherein in step a) the core is prepared by admixing rasagiline base, citric acid and malic acid, and a pharmaceutically acceptable excipient. 
     
     
         16 . The dosage form of  claim 1 , wherein in step b) the core is coated with methacrylic acid-ethyl acrylate copolymer (1:1) and a plasticizer. 
     
     
         17 . The dosage form of  claim 16 , wherein in step b) the ratio of methacrylic acid-ethyl acrylate copolymer (1:1) to the plasticizer in the outer one of the two coating layers is between 10 to 1 and 2 to 1. 
     
     
         18 . The dosage form of  claim 17 , wherein in step b) the ratio of methacrylic acid-ethyl acrylate copolymer (1:1) to the plasticizer in the outer one of the two coating layers is 5 to 1. 
     
     
         19 . The dosage form of  claim 16 , wherein in step b) the plasticizer is triethyl citrate. 
     
     
         20 . The dosage form of  claim 1 , wherein in step b) the acid resistant coating comprises two coating layers. 
     
     
         21 . The dosage form of  claim 20 , wherein in step b) the inner one of the two coating layers comprises hypromellose. 
     
     
         22 . The dosage form of  claim 20 , wherein in step b) the outer one of the two coating layers further comprises talc. 
     
     
         23 . The dosage form of  claim 1 , wherein the production process further comprises: c) coating the acid-resistant pharmaceutical coating with a pharmaceutically acceptable film coating. 
     
     
         24 . The dosage form of  claim 23 , wherein the pharmaceutically acceptable film coating is Opadry II OY-GM-28900 White, or Opadry II Y-30-18037 White, and/or Opadry fx 63f97546 silver. 
     
     
         25 . The dosage form of  claim 23 , wherein the pharmaceutically acceptable film coating is Opadry II 31F20721 Blue, or Opadry II 34G24627 Pink and/or Opadry fx 63f97546 silver.