Pharmaceutical composition for once-a-day oral administration of trospium chloride

Abstract

A pharmaceutical composition of a pharmaceutically acceptable trospium salt, with upon administration to a human patient generates an average steady state blood levels of trospium with a minimum (C min ) and maximum (C max ) blood levels of about 0.5-2.5 ng/ml and about 2.0-6.0 ng/ml, respectively.

1 - 77 . (canceled) 
     
     
         78 . A pharmaceutical composition suitable for a once-a-day oral administration of trospium chloride to a human, the composition comprising:
 a. a plurality of particulates comprising trospium chloride,   b. said particulates further comprising at least one polymer,   c. said pharmaceutical composition having an in vitro release profile as measured by USP Apparatus II, 50 RPM, at 37° C., in an acidic medium of 750 mL 0.1 N HCl for the first 2 hours and then adjusting the medium to pH 7.5 at 2 hours using phosphate buffer;   d. whereby said in vitro profile is characterized by a release of up to about 20% of the total trospium chloride during the first two hours in the acidic medium, and a release of between about 60% and about 80% of the total trospium chloride about 2 hours after said pH adjustment.   
     
     
         79 . The pharmaceutical composition of  claim 78 , comprising an ethylcellulose polymer. 
     
     
         80 . The pharmaceutical composition of  claim 78 , comprising a polymer selected from the group consisting of a copolymer of acrylic and methacrylic acid esters, a copolymer of polyvinylpyrrolidone and vinyl acetate, and cellulose derivatives. 
     
     
         81 . The pharmaceutical composition of  claim 80 , wherein said plurality of particulates comprises at least 30 mg trospium chloride. 
     
     
         82 . The pharmaceutical composition of  claim 80 , wherein said plurality of particulates comprises at least 40 mg trospium chloride. 
     
     
         83 . The pharmaceutical composition of  claim 80 , wherein said plurality of particulates comprises at least 50 mg trospium chloride. 
     
     
         84 . The pharmaceutical composition of  claim 80 , wherein the particulates are substantially spherical. 
     
     
         85 . The pharmaceutical composition of  claim 80 , wherein upon once daily oral administration to a subject in need thereof provides therapeutically effective amounts of trospium chloride to treat said subject's condition while reducing the occurrence of dry-mouth relative to oral, twice-daily administration of 20 mg immediate release trospium chloride tablets. 
     
     
         86 . The pharmaceutical composition of  claim 78 , wherein once-a-day administration of said pharmaceutical composition provides steady state blood levels of trospium chloride less than about 6.0 ng/mL. 
     
     
         87 . The pharmaceutical composition of  claim 78 , wherein once-a-day administration of said pharmaceutical composition provides steady state blood levels of trospium chloride greater than about 0.5 ng/mL. 
     
     
         88 . The pharmaceutical composition of  claim 78 , whereby single-dosage administration of said pharmaceutical composition provides a plasma concentration versus time curve having an area under the curve (AUC 0-72 hrs ) of about 30,000 pg/ml*hr to about 80,000 pg/ml*hr. 
     
     
         89 . The pharmaceutical composition of  claim 78 , whereby single-dosage administration of said pharmaceutical composition provides blood levels of trospium chloride less than about 3.0 ng/mL. 
     
     
         90 . The pharmaceutical composition of  claim 80 , wherein once-a-day administration of said pharmaceutical composition provides steady state blood levels of trospium chloride less than about 6.0 ng/mL. 
     
     
         91 . The pharmaceutical composition of  claim 80 , wherein once-a-day administration of said pharmaceutical composition provides steady state blood levels of trospium chloride greater than about 0.5 ng/mL. 
     
     
         92 . The pharmaceutical composition of  claim 80 , whereby single-dosage administration of said pharmaceutical composition provides a plasma concentration versus time curve having an area under the curve (AUC 0-72 hrs ) of about 30,000 pg/ml*hr to about 80,000 pg/ml*hr. 
     
     
         93 . The pharmaceutical composition of  claim 80 , whereby single-dosage administration of said pharmaceutical composition provides blood levels of trospium chloride less than about 3.0 ng/mL.