TOFACITINIB ORAL SUSTAINED RELEASE DOSAGE FORMS
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Accused Products
Abstract
The present invention relates to oral sustained release formulations of tofacitinib and pharmaceutical acceptable salts thereof. The formulations described herein have desirable pharmacokinetic characteristics.
46 Citations
114 Claims
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14. A once daily pharmaceutical dosage form comprising tofacitinib, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, wherein said dosage form is a sustained release dosage form, and when administered orally to a subject has a mean steady-state minimum plasma concentration (Cmin) less than about 0.3 ng/mL per mg of tofacitinib dosed.
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15. A once daily pharmaceutical dosage form comprising tofacitinib, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, wherein said dosage form is a sustained release dosage form, and when administered orally to a subject has a mean fed/fasted ratio of the area under the plasma concentration versus time curve from about 0.7 to about 1.4 and a mean fed/fasted ratio of the maximum plasma concentration (Cmax) from about 0.7 to about 1.4.
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16. A pharmaceutical dosage form comprising tofacitinib, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, wherein said dosage form is a sustained release dosage form, and when added to a test medium comprising 900 mL of 0.05M pH 6.8 potassium phosphate buffer at 37°
- C. in a standard USP rotating paddle apparatus and the paddles are rotated at 50 rpm, dissolves not more than 30% of the drug in 1 hour, and not less than 35% and not more than 75% of the drug in 2.5 hours and not less than 75% of the tofacitinib in 5 hours.
- 17. A once daily pharmaceutical dosage form comprising tofacitinib, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, wherein the dosage form is a sustained release dosage form and when administered orally to a subject provides an AUC in the range of 80% to 125% of the AUC of an equivalent amount of tofacitinib administered as an immediate release formulation BID and provides a ratio of geometric mean plasma Cmax to Cmin from about 10 to about 100.
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- 65. A once daily pharmaceutical dosage form comprising tofacitinib, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, wherein said dosage form is a sustained release dosage form, and when administered to a subject has a mean area under the plasma concentration versus time curve following administration from about 17 ng-hr/mL per mg of tofacitinib dosed to about 42 ng-hr/mL per mg of tofacitinib dosed and a ratio of geometric mean plasma Cmax to Cmin from about 10 to about 100.
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97. The sustained release pharmaceutical dosage form of claim wherein the matrix of the dosage form comprises hydroxypropyl methylcellulose.
Specification