Extended release composition containing tramadol

Abstract

The present invention relates to a once daily extended release pharmaceutical preparation of Tramadol or its acceptable pharmaceutical salts. The preparation provides, effective blood concentration for a period of about 24 hours with reduced peak concentrations. It is characterized that effective Tramadol levels appear within the first hours after administration, the time to maximal Tramadol content T max is at least 10 hours and the peak Tramadol concentration is less than three times the concentration obtained after 24 hours of said administration.

1 . Oral Tramadol pharmaceutical composition suitable for once daily administration comprising an effective amount of Tramadol or its pharmaceutically acceptable salts providing in vivo, a time of Tramadol peak plasma concentration (T max ) greater than 10 hours and a peak Tramadol plasma concentrations (C max ) which are less than three times the plasma concentration obtained 24 hours after administration (C 24h ) of a single dose of such composition. 
     
     
         2 . Compositions of  claim 1  wherein said pharmaceutical composition provides after repeated once daily administration in vivo, a time of Tramadol peak plasma concentration (T max ) greater than 10 hours and a peak Tramadol plasma concentrations (C max ) which are not more than three times the plasma concentration obtained 24 hours of administration (C 24h ). 
     
     
         3 . Composition of  claim 1  wherein said pharmaceutical composition provides, after single administration in vivo, o-demethyl Tramadol peak plasma concentrations (C max ) which are not more than twice the plasma concentration obtained 24 hours after administration (C 24h ). 
     
     
         4 . Composition of  claim 1  wherein said pharmaceutical composition provides, after repeated once daily administrations, o-demethyl Tramadol peak plasma concentrations (C max ) which are not more than twice the plasma concentration obtained 24 hours after administration (C 24h ). 
     
     
         5 . Composition of  claim 1  wherein said pharmaceutical composition provides, after single administration in vivo, a time of o-demethyl Tramadol peak plasma concentration (T max ) greater than 10 hours. 
     
     
         6 . Composition of  claim 1  wherein said pharmaceutical, composition provides, after repeated once daily administrations in vivo, a time of o-demethyl Tramadol peak plasma concentrations (T max ) greater than 10 hours. 
     
     
         7 . Composition of  claim 1  wherein said pharmaceutical composition exhibit an in vitro dissolution biphasic profile. 
     
     
         8 . Composition of  claim 1  wherein said pharmaceutical composition comprises individual containing Tramadol units from which Tramadol is released at different rates. 
     
     
         9 . Composition of  claim 10  wherein said pharmaceutical composition comprises at least one individual unit from which about 80% of Tramadol is released within about 6 hours. 
     
     
         10 . Composition of  claim 10  wherein said pharmaceutical composition comprises at least one individual unit from which about 80% of Tramadol is released within 1 hour. 
     
     
         11 . Composition of  claim 1  wherein said pharmaceutical composition comprises sustained released beads covered by layers containing Tramadol from which the Tramadol is released at a different rate than from the sustained release beads. 
     
     
         12 . Composition of  claim 13  wherein said pharmaceutical composition comprises layers containing Tramadol from which at least 80% of Tramadol is released within about 6 hours. 
     
     
         13 . Composition of  claim 13  wherein said pharmaceutical composition comprises layers containing Tramadol from which at least 80% of Tramadol is released within about 1 hour. 
     
     
         14 . Composition of  claim 10  wherein said pharmaceutical composition is characterized in vivo, by a rapid rise of Tramadol plasma concentration. 
     
     
         15 . Composition of  claim 16  wherein said rapid Tramadol plasma concentration rise occurs within about 0.5 to 3 hours after administration. 
     
     
         16 . Composition of  claim 16  wherein said rapid Tramadol plasma is less than the peak concentration (C max ) measured between successive administration. 
     
     
         17 . Composition of  claim 1  wherein pharmaceutical composition comprises multiple Tramadol containing units contained in a capsule. 
     
     
         18 . Composition of  claim 1  wherein said pharmaceutical composition comprises multiple Tramadol containing units compressed in a tablet. 
     
     
         19 . Composition of  claim 1  wherein said pharmaceutical composition provides similar pharmaceutical profile when such composition is administered orally with or without food. 
     
     
         20 . Composition of  claim 1  wherein said pharmaceutical composition provides effective pain control in humans during a period of about 24 hours after administration. 
     
     
         21 . Composition of  claim 1 , wherein said pharmaceutical composition provides effective pain control in humans, starting at about 1 to 2 hours after administration and lasting for about 24 hours after administration. 
     
     
         22 . Composition of  claim 1 , which exhibits a biphasic absorption profile in vivo under fed and fasted administration conditions. 
     
     
         23 . Composition of  claim 1 , wherein a first C max  obtained from said fast release tablet is less than a second C max  obtained from said slow release beads. 
     
     
         24 . A method of managing post-surgery pain control, which comprises the step of administering the composition of  claim 1 , to a patient in need thereof. 
     
     
         25 . The method of  claim 24 , wherein said managing is effected under fed and fasted administration conditions. 
     
     
         26 . The method of  claim 24 , wherein said administering is once daily.