Diclofenac Formulations and Methods of Use

Abstract

Methods and formulations are provided for treating migraine and other acute pain episodes using diclofenac, and formulations of diclofenac that provide both rapid and sustained relief from acute pain. Methods and formulations are also provided for treating symptoms that often accompany migraine and acute pain such as photophobia, phonophobia, nausea and vomiting.

1 ) A method of treating phonophobia and photophobia in a human patient comprising: a) providing an oral formulation comprising one or more pharmaceutically acceptable excipients and 50 mg. of diclofenac or a pharmaceutically acceptable salt thereof, wherein said formulation achieves a C max  of from about 1500 to about 2500 ng/ml and t max  in from about 10 to about 25 minutes; and b) orally administering said formulation to a patient suffering from phonophobia and photophobia wherein said t max  and C max  are mean values obtained from a plurality of human patients. 
   
   
       2 ) The method of  claim 1  wherein said patient is diagnosed as suffering from migraine requiring sustained migraine relief for at least 24 hours. 
   
   
       3 ) The method of  claim 1  wherein said formulation comprises about 50 mg. of diclofenac potassium, and greater than 20 wt. % of an alkali metal carbonate or bicarbonate based on the weight of the acid form of diclofenac. 
   
   
       4 ) The method of  claim 1  wherein said formulation achieves t max  in from about 10 to about 20 minutes. 
   
   
       5 ) A method of treating recurrent migraine in a human patient suffering from migraine comprising: a) providing an oral formulation comprising one or more pharmaceutically acceptable excipients and 50 mg. of diclofenac or a pharmaceutically acceptable salt thereof, wherein said formulation achieves a C max  of from about 1500 to about 2500 ng/ml and t max  in from about 10 to about 25 minutes; and b) orally administering said formulation to a patient requiring sustained migraine relief for at least 24 hours. 
   
   
       6 ) The method of  claim 5  wherein said patient suffers from photophobia and phonophobia. 
   
   
       7 ) The method of  claim 5  wherein said liquid formulation comprises about 50 mg. of diclofenac potassium, and greater than 20 wt. % of an alkali metal carbonate or bicarbonate based on the weight of the acid form of diclofenac. 
   
   
       8 ) The method of  claim 5  wherein said C max  has an inter-subject variability of less than about 70%. 
   
   
       9 ) The method of  claim 5  wherein said t max  has an inter-subject variability of less than about 70%. 
   
   
       10 ) The method of  claim 5  wherein said formulation achieves t max  in from about 10 to about 20 minutes. 
   
   
       11 ) A method of treating headache pain, nausea, photophobia and phonophobia in a human patient comprising: a) providing an oral formulation comprising one or more pharmaceutically acceptable excipients and 50 mg. of diclofenac or a pharmaceutically acceptable salt thereof, wherein said formulation achieves a C max  of from about 1500 to about 2500 ng/ml and t max  in from about 10 to about 25 minutes; and b) orally administering said formulation to a patient suffering from of headache pain, nausea, photophobia and phonophobia. 
   
   
       12 ) (canceled) 
   
   
       13 ) The method of  claim 11  further comprising diagnosing said patient suffering from migraine as requiring sustained migraine relief for at least 24 hours. 
   
   
       14 ) The method of  claim 11  wherein said C max  has an inter-subject variability of less than about 70%. 
   
   
       15 ) The method of  claim 11  wherein said t max  has an inter-subject variability of less than about 70%. 
   
   
       16 ) The method of  claim 11  wherein said liquid formulation comprises about 50 mg. of diclofenac potassium, and greater than 20 wt. % of an alkali metal carbonate or bicarbonate based on the weight of the acid form of diclofenac. 
   
   
       17 ) The method of  claim 11  wherein said formulation achieves t max  in from about 10 to about 20 minutes. 
   
   
       18 ) A method of treating acute pain in a human patient requiring pain relief for at least eight hours, comprising: a) providing an oral formulation comprising one or more pharmaceutically acceptable carriers and about 50 mg. of diclofenac or a pharmaceutically acceptable salt thereof, wherein said formulation: i) achieves a C max  of from about 1400 to about 2500 ng/ml; and ii) achieves t max  in from about 10 to about 35 minutes; and b) orally administering said formulation to a patient suffering from acute pain, no more than 3 total times in a 24 hour period. 
   
   
       19 ) The method of  claim 18  wherein said formulation achieves t max  in from about 10 to about 30 minutes. 
   
   
       20 ) The method of  claim 18  wherein said acute pain is post-operative dental pain. 
   
   
       21 ) The method of  claim 18  wherein said liquid formulation comprises about 50 mg. of diclofenac potassium, and greater than 20 wt. % of an alkali metal carbonate or bicarbonate based on the weight of the acid form of diclofenac. 
   
   
       22 )- 50 ) (canceled)