Diclofenac formulations and methods of use

• US 8,097,651 B2
• Filed: 01/07/2010
• Issued: 01/17/2012
• Est. Priority Date: 06/17/2005
• Status: Active Grant

• Current Assignee: APR Applied Pharma Research SA (RELIEF THERAPEUTICS Holding SA)
• Original Assignee: APR Applied Pharma Research SA (RELIEF THERAPEUTICS Holding SA)
• Inventors: Reiner, Giorgio, Reiner, Alberto, Meyer, Andreas
• Primary Examiner(s): Crane, Lawrence E
• Application Number:
  US12/683,517
• Publication Number:
  US 20100204330A1
• Time in Patent Office: 740 Days
• Field of Search: None
• US Class Current: 514/553
• CPC Class Codes: A61K 31/196 the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61K 9/0095 Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches A61K9/0007 takes precedence; eatable gels or foams A61K9/0056; oral mucosa adhesive forms A61K9/006
• CPC Class Codes: A61K 9/08 Solutions composition of solutions A61K47/00
• CPC Class Codes: A61K 9/14 Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles microspheres A61K9/16; microcapsules A61K9/50; nanocapsules, nanoparticles of the matrix type A61K9/51
• CPC Class Codes: A61K 9/145 with organic compounds
• CPC Class Codes: A61K 9/1623 Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

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.

Claims

1. A method of treating phonophobia and photophobia in a human patient in need thereof 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 one or more pharmaceutically acceptable excipients comprises a buffering or alkalizing agent, further wherein said formulation has been shown to achieve 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 said buffering or alkalizing agent comprises 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 has been shown to achieve t_max in from about 10 to about 20 minutes.

5. The method of claim 1, wherein said alkaline buffering agent or alkalizing agent is present relative to said diclofenac at a weight ratio of less than about 5:

1.

6. A method of treating recurrent migraine in a human patient in need thereof 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 one or more pharmaceutically acceptable excipients comprises a buffering or alkalizing agent, further wherein said formulation has been shown to achieve 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.

7. The method of claim 6 wherein said patient suffers from photophobia and phonophobia.

8. The method of claim 6 wherein said formulation comprises about 50 mg. of diclofenac potassium, and said buffering or alkalizing agent comprises greater than 20 wt. % of an alkali metal carbonate or bicarbonate based on the weight of the acid form of diclofenac.

9. The method of claim 6 wherein said C_max has been shown to have an inter-subject variability of less than about 70%.

10. The method of claim 6 wherein said t_max has been shown to have an inter-subject variability of less than about 70%.

11. The method of claim 6 wherein said formulation has been shown to achieve t_max in from about 10 to about 20 minutes.

12. The method of claim 6, wherein said alkaline buffering agent or alkalizing agent is present relative to said diclofenac at a weight ratio of less than about 5:

1.

13. A method of treating headache pain, nausea, photophobia and phonophobia in a human patient in need thereof 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 one or more pharmaceutically acceptable excipients comprise a buffering or alkalizing agent wherein said formulation has been shown to achieve 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 headache pain, nausea, photophobia and phonophobia.

14. The method of claim 13 further comprising diagnosing said patient suffering from migraine as requiring sustained migraine relief for at least 24 hours and treating recurrent migraine in said patient over a period of 24 hours.

15. The method of claim 13 wherein said C_max has been shown to have an inter-subject variability of less than about 70%.

16. The method of claim 13 wherein said t_max has been shown to have an inter-subject variability of less than about 70%.

17. The method of claim 13 wherein said formulation comprises about 50 mg. of diclofenac potassium, and said alkaline buffering agent or alkalizing agent comprises greater than 20 wt. % of an alkali metal carbonate or bicarbonate based on the weight of the acid form of diclofenac.

18. The method of claim 13 wherein said formulation has been shown to achieve t_max in from about 10 to about 20 minutes.

19. The method of claim 13, wherein said alkaline buffering agent or alkalizing agent is present relative to said diclofenac at a weight ratio of less than about 5:

1.