Extended Release Compositions and Methods for Their Manufacture

A formulation comprising quetiapine or a pharmaceutically acceptable salt thereof wherein the quetiapine content is about 25.6 to about 26.5% by weight and wherein the dosage form comprises about 30% hydroxypropyl methylcellulose by weight and about 12.5% sodium citrate dihydrate by weight.

A formulation comprising quetiapine or a pharmaceutically acceptable salt thereof wherein the quetiapine content is about 32.9% to about 33.8% by weight and wherein the dosage form comprises about 12.5% sodium citrate dihydrate by weight and about 30% hydroxypropyl methylcellulose by weight.

A formulation comprising quetiapine or a pharmaceutically acceptable salt thereof wherein the quetiapine content is about 37.1% to about 38.0% by weight and wherein the dosage form comprises about 12.5% sodium citrate dihydrate by weight and about 30% hydroxypropyl methylcellulose by weight and wherein about 15 to about 29 of the 30% hydroxypropyl methylcellulose is a first hydroxypropyl methylcellulose constituent;

• the remainder of the 30% is a second hydroxypropyl methylcellulose constituent;
• and the first and second constituents correspond, respectively, to a first hydroxypropyl methylcellulose grade that has a apparent viscosity between about 80 cp and about 120 cp and a second hydroxypropyl methylcellulose that has an apparent viscosity between about 3000 cp and about 5600 cp,wherein the ratio of the first hydroxypropyl methylcellulose grade to the second hydroxypropyl methylcellulose grade is not 25.0 to 5.0.

A formulation comprising quetiapine or a pharmaceutically acceptable salt thereof wherein the quetiapine content is about 45.5% to about 46.4% by weight and wherein the dosage form comprises about 11.5% sodium citrate dihydrate by weight and about 30% hydroxypropyl methylcellulose by weight.

A method of effectively treating psychoses in humans, comprising orally administering to a human patient on a once-a-day basis an oral extended release dosage form containing quetiapine or a pharmaceutically acceptable salt thereof wherein the quetiapine content is 50 mg which at steady-state provides a time to maximum plasma concentration (tmax) of said antipsychotic in about 2 to about 16 hours, a maximum plasma concentration (Cmax) which is greater than or equal to four times the plasma concentration of said antipsychotic at about 24 hours, and which dosage form provides effective treatment of psychoses for about 24 hours or more after administration to the patient.

A method of effectively treating psychoses in humans, comprising orally administering to a human patient on a once-a-day basis an oral extended release dosage form containing quetiapine or a pharmaceutically acceptable salt thereof wherein the quetiapine content is 150 mg which at steady-state provides a time to maximum plasma concentration (tmax) of said antipsychotic in about 2 to about 16 hours, a maximum plasma concentration (Cmax) which is greater than or equal to four times the plasma concentration of said antipsychotic at about 24 hours, and which dosage form provides effective treatment of psychoses for about 24 hours or more after administration to the patient.

A method of effectively treating psychoses in humans, comprising orally administering to a human patient on a once-a-day basis an oral extended release dosage form containing quetiapine or a pharmaceutically acceptable salt thereof wherein the quetiapine content is 200 mg which at steady-state provides a time to maximum plasma concentration (tmax) of said antipsychotic in about 2 to about 8 hours, a maximum plasma concentration (Cmax) which is greater than or equal to four times the plasma concentration of said antipsychotic at about 24 hours, and which dosage form provides effective treatment of psychoses for about 24 hours or more after administration to the patient.

A method of effectively treating psychoses in humans, comprising orally administering to a human patient on a once-a-day basis an oral extended release dosage form containing quetiapine or a pharmaceutically acceptable salt thereof wherein the quetiapine content is 400 mg which at steady-state provides a time to maximum plasma concentration (tmax) of said antipsychotic in about 3 to about 8 hours, a maximum plasma concentration (Cmax) which is greater than or equal to four times the plasma concentration of said antipsychotic at about 24 hours, and an area under curve between the time of administration and 24 hours after administration (AUCcum, 24) which is greater than or equal to about 6000 ng.hr/mL, and which dosage form provides effective treatment of psychoses for about 24 hours or more after administration to the patient.