Controlled release tramadol formulations

Abstract

A controlled release preparation for oral administration contains tramadol, or a pharmaceutically acceptable salt thereof, as active ingredient.

1 . A solid controlled release oral dosage form, comprising:
 a therapeutically effective amount of tramadol or a pharmaceutically acceptable salt thereof incorporated into a controlled release matrix,   said controlled release matrix comprising an alkylcellulose or an acrylic resin or a mixture thereof;   said dosage form providing a therapeutic effect for at least about 24 hours.   
   
   
       2 . The controlled release dosage form as claimed in  claim 1 , wherein said controlled release matrix comprises a polymethacrylate. 
   
   
       3 . The controlled release dosage form as claimed in  claim 1 , wherein said controlled release matrix comprises a water insoluble cellulose. 
   
   
       4 . The controlled release dosage form as claimed in  claim 2 , wherein said controlled release matrix further comprises a water soluble cellulose. 
   
   
       5 . The controlled release dosage form as claimed in  claim 3 , wherein said controlled release matrix further comprises a polyvinylpyrrolidone. 
   
   
       6 . The controlled release dosage form as claimed in  claim 1 , comprising from about 50 to 800 mg of tramadol or a pharmaceutically acceptable salt thereof, calculated as the hydrochloride salt. 
   
   
       7 . The controlled release dosage form as claimed in  claim 1 , having a dissolution rate in-vitro when measured using the Ph. Eur. Paddle Method at 100 rpm in 900 ml 0.1N hydrochloric acid at 37° C. and using UV detection at 270 nm, from about 0 to about 50% tramadol released after 1 hour; from about 0 to about 75% tramadol released after 2 hours; from about 10 to about 95% tramadol released after 4 hours; from about 35 to about 100% after 8 hours; from about 55 to about 100% tramadol released after 12 hours; from about 70 to about 100% tramadol released after 16 hours; and greater than 90% tramadol released after 24 hours, by weight. 
   
   
       8 . The controlled release dosage form as claimed in  claim 1 , having a dissolution rate in-vitro when measured using the Ph. Eur. Paddle Method at 100 rpm in 900 ml 0.1N hydrochloric acid at 37° C. and using UV detection at 270 nm, from about 0 to about 30% tramadol released after 1 hour; from about 0 to about 40% tramadol released after 2 hours; from about 3 to about 55% tramadol released after 4 hours; from about 10 to about 65% after 8 hours; from about 20 to about 75% tramadol released after 12 hours; from about 30 to about 88% tramadol released after 16 hours; from about 50 to about 100% tramadol released after 24 hours and greater than 80% tramadol released after 36 hours, by weight. 
   
   
       9 . The controlled release dosage form as claimed in  claim 1 , having a dissolution rate in-vitro when measured using the Ph. Eur. Paddle Method at 100 rpm in 900 ml 0.1N hydrochloric acid at 37° C. and using UV detection at 270 nm, from about 15 to about 25% tramadol released after 1 hour; from about 25 to about 35% tramadol released after 2 hours; from about 30 to about 45% tramadol released after 4 hours; from about 40 to about 60% after 8 hours; from about 55 to about 70% tramadol released after 12 hours; and from about 60 to about 75% tramadol released after 16 hours, by weight. 
   
   
       10 . The dosage form according to  claim 1 , which provides a T max  from about 3 to about 6 hours. 
   
   
       11 . The dosage form according to  claim 1 , which provides a W 50  from about 10 to about 33 hours. 
   
   
       12 . The dosage form according to  claim 3  wherein said water insoluble cellulose comprises ethylcellulose. 
   
   
       13 . The dosage form of  claim 1 , comprising 100 mg tramadol hydrochloride. 
   
   
       14 . The dosage form of  claim 1 , comprising 200 mg tramadol hydrochloride. 
   
   
       15 . The dosage form of  claim 1 , comprising 300 mg tramadol hydrochloride. 
   
   
       16 . The dosage form of  claim 1 , comprising 400 mg tramadol hydrochloride. 
   
   
       17 . The dosage form of  claim 1 , comprising 600 mg tramadol hydrochloride. 
   
   
       18 . The dosage form of  claim 1 , further comprising a coating. 
   
   
       19 . The dosage form of  claim 18 , wherein the coating is a film coating. 
   
   
       20 . The dosage form of  claim 1 , wherein said controlled release matrix is in a form of multiparticulates.