Celecoxib compositions

Abstract

Pharmaceutical compositions are provided comprising one or more orally deliverable dose units, each comprising particulate celecoxib in an amount of about 10 mg to about 1000 mg in intimate mixture with one or more pharmaceutically acceptable excipients. The compositions are useful in treatment or prophylaxis of cyclooxygenase-2 mediated conditions and disorders.

1 . A pharmaceutical composition comprising one or more orally deliverable dose units, each comprising particulate celecoxib in an amount of about 10 mg to about 1000 mg in intimate mixture with one or more pharmaceutically acceptable excipients, wherein a single dose unit, upon oral administration to a fasting subject, provides a time course of blood serum concentration of celecoxib having at least one of
 (a) a time to reach 100 ng/ml not greater than about 0.5 h after administration;   (b) a time to reach maximum concentration (T max ) not greater than about 3 h after administration;   (c) a duration of time wherein concentration remains above 100 ng/ml not less than about 12 h;   (d) a terminal half-life (T 1/2 ) not less than about 10 h; and   (e) a maximum concentration (C max ) not less than about 200 ng/ml.   
     
     
         2 . The composition of  claim 1  wherein the amount of celecoxib in each dose unit is about 50 mg to about 800 mg. 
     
     
         3 . The composition of  claim 1  wherein the amount of celecoxib in each dose unit is about 75 mg to about 400 mg. 
     
     
         4 . The composition of  claim 1  wherein the amount of celecoxib in each dose unit is about 100 mg to about 200 mg. 
     
     
         5 . A composition of  claim 1  that is suitable, by oral administration to a subject of a dose unit once or twice a day, for providing therapeutically or prophylactically effective inhibition of cyclooxygenase-2. 
     
     
         6 . A composition of  claim 1  that is suitable, by oral administration to a subject of a dose unit once or twice a day, for treatment or prophylaxis of a cyclooxygenase-2 mediated condition or disorder. 
     
     
         7 . A composition of  claim 1  in the form of unit dosage capsules or tablets. 
     
     
         8 . The composition of  claim 7  wherein said excipient(s) are selected from the group consisting of pharmaceutically acceptable diluents, disintegrants, binding agents, wetting agents and lubricants. 
     
     
         9 . The composition of  claim 7  wherein said excipient(s) include one or more pharmaceutically acceptable diluents in a total amount of about 5% to about 99% by weight of the composition. 
     
     
         10 . The composition of  claim 7  wherein said excipients include one or more pharmaceutically acceptable disintegrants in a total amount of about 0.2% to about 30% by weight of the composition. 
     
     
         11 . The composition of  claim 7  wherein said excipients include one or more pharmaceutically acceptable binding agents in a total amount of about 0.5% to about 25% by weight of the composition. 
     
     
         12 . The composition of  claim 7  wherein said excipients include one or more pharmaceutically acceptable wetting agents in a total amount of about 0.25% to about 15% by weight of the composition. 
     
     
         13 . The composition of  claim 7  wherein said excipients include one or more pharmaceutically acceptable lubricants in a total amount of about 0.1% to about 10% by weight of the composition. 
     
     
         14 . A composition of  claim 7  comprising
 (a) one or more pharmaceutically acceptable diluents in a total amount of about 10% to about 85% by weight of the composition; 
 (b) one or more pharmaceutically acceptable disintegrants in a total amount of about 0.2% to about 10% by weight of the composition; and 
 (c) one or more pharmaceutically acceptable binding agents in an amount of about 0.5% to about 10% by weight of the composition. 
 
     
     
         15 . A composition of  claim 14  further comprising
 (d) one or more pharmaceutically acceptable wetting agents in a total amount of about 0.4% to about 10% by weight of the composition; and/or 
 (e) one or more pharmaceutically acceptable lubricants in a total amount of about 0.2% to about 8% by weight of the composition. 
 
     
     
         16 . The composition of  claim 7  wherein celecoxib is present in an amount of about 1% to about 95% by weight of the composition. 
     
     
         17 . A composition of  claim 7  comprising unit dosage capsules or tablets each providing a 100 mg or 200 mg dose of celecoxib. 
     
     
         18 . A composition of  claim 7  prepared by a process wherein the celecoxib, together with one or more excipients, is directly encapsulated or directly compressed into tablets. 
     
     
         19 . A composition of  claim 7  prepared by a process wherein the celecoxib, together with one or more excipients, is wet granulated prior to encapsulation or compression into tablets. 
     
     
         20 . A composition of  claim 7  prepared by a process wherein the celecoxib, together with one or more excipients, is dry granulated prior to encapsulation or compression into tablets. 
     
     
         21 . A composition of  claim 1  providing, upon oral ingestion, a therapeutic effect as a cyclooxygenase-2 inhibitor over an interval of about 12 to about 24 h after ingestion. 
     
     
         22 . The composition of  claim 1  wherein, upon oral ingestion, at least about 50% of the celecoxib is released, as determined in vitro, within about 15 minutes after ingestion. 
     
     
         23 . A composition of  claim 1  further comprising one or more opioid or analgesic drugs. 
     
     
         24 . A method of treating a medical condition or disorder in a subject where treatment with a cyclooxygenase-2 inhibitor is indicated, comprising orally administering to the subject a composition of  claim 1  once or twice a day. 
     
     
         25 . A method of preparing a composition of  claim 7  comprising
 (a) wet granulating celecoxib together with one or more excipients to form a wet granulated mixture; 
 (b) drying the wet granulated mixture; and 
 (c) encapsulating the dried granulated mixture or compressing the dried granular mixture into tablets.