PHARMACEUTICAL COMPOSITION FOR ONCE-A-DAY ORAL ADMINISTRATION OF TROSPIUM CHLORIDE
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 first plurality of particulates comprising trospium chloride, said first plurality of particulates further comprising a first polymer,
a second plurality of particulates comprising trospium chloride, said second plurality of particulates further comprising a second polymer,
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;
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 , wherein the second polymer comprises ethylcellulose.
80 . The pharmaceutical composition of claim 78 , wherein the first polymer comprises a methacrylic acid copolymer.
81 . The pharmaceutical composition of claim 80 , wherein the second polymer comprises ethylcellulose.
82 . The pharmaceutical composition of claim 81 , wherein said first plurality of particulates comprises about 30 mg trospium chloride and said second plurality of particulates comprises about 30 mg trospium chloride.
83 . The pharmaceutical composition of claim 82 , wherein the particulates are substantially spherical.
84 . The pharmaceutical composition of claim 82 , wherein 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.
85 . The pharmaceutical composition of claim 78 , wherein the first polymer is selected from the group consisting of a methacrylic acid copolymer, cellulose acetate phthalate, hydroxypropyl methylcellulose phthalate, and polyvinyl acetate phthalate, and wherein the second polymer is selected from the group consisting of a copolymer of acrylic and methacrylic acid esters, a copolymer of polyvinylpyrrolidone and vinyl acetate, and cellulose derivatives.
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 85 , 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 85 , 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 85 , 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 85 , whereby single-dosage administration of said pharmaceutical composition provides blood levels of trospium chloride less than about 3.0 ng/mL.