Methods and compositions for treating migraine and conditions associated with pain

Abstract

The present invention relates to pharmaceutical compositions of an non-steroidal anti-inflammatory drug (NSAIDs) such as, aspirin, diclofenac, ibuprofen, ketoprofen, or naproxen, or any pharmaceutically acceptable salts, solvates, or prodrugs thereof, and the medical use of these compositions. The compositions, which can be formulated for topical administration, can provide extended release of the NSAIDs. The compositions of the invention are useful, for example, in the prophylactic treatment or treatment and/or reduction of pain, in the prophylactic treatment or treatment of headaches such as migraine headaches and symptoms of migraine headaches, and in the treatment of temporomandibular disorders (TMD).

What is claimed is: 
     
         1 . A method of treating a temporomandibular disorder (TMD) in a subject in need thereof, said method comprising topically administering to said subject a sustained release composition comprising from about 0.5% (w/w) to about 5% (w/w) of a therapeutic agent and a dermatologically acceptable excipient, wherein said composition is in an amount effective to treat said temporomandibular disorder (TMD) in said subject and wherein administration of said composition to said subject results in a peak plasma concentration of said therapeutic agent at three hours that is at most about 450 ng/mL 
     
     
         2 . The method of  claim 1 , wherein said peak plasma concentration of said therapeutic agent when administered topically is lower than the peak plasma concentration of said therapeutic agent when administered orally. 
     
     
         3 . The method of  claim 1 , wherein administration of said composition to said subject provides for gradual release of said therapeutic agent over 2-24 hours. 
     
     
         4 . The method of  claim 3 , wherein administration of said composition results in a plasma concentration of said therapeutic agent that is maintained between about 50 ng/mL and about 150 ng/mL for up to 24 hours. 
     
     
         5 . The method of  claim 1 , wherein the half-life of said therapeutic agent is from about 7 to about 13 hours. 
     
     
         6 . The method of  claim 1 , further comprising monitoring whether the subject experiences amelioration of a symptom of TMD. 
     
     
         7 . The method of  claim 6 , wherein said symptom of TMD is selected from the group consisting of: a toothache, headache, neck ache, dizziness, earache, upper shoulder pain, tenderness in the face, pain in the temporomandibular joint or its surrounding tissues, functional limitations of the mandible, clicking in the temporomandibular joint during motion, and swelling of the face. 
     
     
         8 . The method of  claim 1 , wherein said therapeutic agent is a non-steroidal anti-inflammatory drug (NSAID) or a pharmaceutically acceptable salt thereof. 
     
     
         9 . The method of  claim 8 , wherein said NSAID or a pharmaceutically acceptable salt thereof is selected from the group consisting of: aspirin, choline and magnesium salicylates and salts thereof, celecoxib, diclofenac and salts thereof, diflunisal, etodolac, fenoprofen and salts thereof, flurbiprofen, ibuprofen, indomethacin, ketoprofen, meclofenamate and salts thereof, mefenamic acid, meloxicam, nabumetone, naproxen and salts thereof, oxaprozin, piroxicam, rofecoxib, salsalate, sulindac, tolmetin and salts thereof, and valdecoxib. 
     
     
         10 . The method of  claim 8 , wherein said NSAID or a pharmaceutically acceptable salt thereof is ketoprofen. 
     
     
         11 . The method of  claim 10 , wherein said composition comprises from about 20 mg to about 200 mg of ketoprofen in unit dosage form. 
     
     
         12 . The method of  claim 10 , wherein said composition comprises a total maximum dosage of about 135 mg of ketoprofen. 
     
     
         13 . The method of  claim 1 , wherein said composition is formulated as a gel, cream, lotion, ointment, foam, powder, solution, spray, emulsion, or suspension for topical administration. 
     
     
         14 . The method of  claim 13 , wherein said composition if formulated as a gel for topical administration. 
     
     
         15 . The method of  claim 1 , wherein said composition is administered one or more times a day. 
     
     
         16 . The method of  claim 1 , wherein said composition is administered for one day or at least two to twenty days. 
     
     
         17 . The method of  claim 1 , wherein said composition is administered for more than twenty days. 
     
     
         18 . The method of  claim 1 , wherein said composition is administered with a second agent. 
     
     
         19 . The method of  claim 18 , wherein said second agent is selected from the group consisting of: a corticosteroid, acetaminophen, an opioid, a muscle relaxant, an anti-anxiety drug, an anti-depressant, an anti-convulsant drug, an antipsychotic, an antiepileptic drug, and a selective serotonin reuptake inhibitor (SSRI).