Claims for Patent: 9,827,197

Summary for Patent: 9,827,197

Title:	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.
Inventor(s):	Reiner; Giorgio (Como, IT), Reiner; Alberto (Como, IT), Meyer; Andreas (Neuenburg, DE)
Assignee:	APR APPLIED PHARMA RESEARCH SA (Balerna, CH)
Application Number:	14/534,428
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,827,197
Patent Claims:	1. A pharmaceutical formulation comprising mannitol and diclofenac or a pharmaceutically acceptable salt thereof in a particulate form at a weight ratio of greater than about 1.5:1, wherein: a) said mannitol comprises a fine diluent having an average particle size of between 10 and 180 micrometers, at a weight ratio of fine diluent to diclofenac in the range from 1:2 to 5:1; b) said mannitol further comprises a coarse diluent having an average particle diameter of between 75 and 300 micrometers, at a weight ratio of coarse diluent to diclofenac in the range from 10:1 to 20:1. 2. The formulation of claim 1, in a unit dose pack, wherein said pack comprises 900 mg. of said formulation, said diclofenac is in the form of diclofenac potassium, and said formulation comprises 50 or 25 or 12.5 mg. of diclofenac potassium. 3. The formulation of claim 1, wherein: a) said diclofenac is in the form of diclofenac potassium, b) said formulation comprises fine mannitol and diclofenac potassium at a weight ratio of from about 1:1 to about 2:1, and c) said fine mannitol has an average particle size of from about 20 to about 80 micrometers. 4. The formulation of claim 1 wherein said diclofenac is in the form of diclofenac potassium, comprising: a) about 50, 25 or 12.5 mg. of diclofenac potassium per 900 mg. of said formulation; b) from about 50 to about 100 mg. of fine mannitol per 900 mg. of said formulation; and c) from about 600 to about 700 mg. of coarse mannitol per 900 mg. of said formulation. 5. The formulation of claim 1 wherein said formulation comprises from about 50 to about 90 wt. % of said mannitol. 6. The formulation of claim 1 wherein said formulation is sugar-free. 7. The formulation of claim 1 wherein said formulation further comprises glyceryl dibehenate. 8. The formulation of claim 1 wherein said formulation further comprises an alkali metal bicarbonate at a weight ratio to said diclofenac of greater than about 1:5. 9. The formulation of claim 1 wherein said formulation further comprises an alkali metal bicarbonate at a weight ratio to said diclofenac of from about 1:5 to about 5:1. 10. The formulation of claim 1 wherein said formulation comprises less than 1.5% water. 11. The formulation of claim 1 wherein said diclofenac is present in a granulate. 12. The formulation of claim 1 wherein said formulation has an average pH of 7.5 when dissolved in 50 ml. of water. 13. The formulation of claim 1 wherein at least 75% of said formulation dissolves completely in 50 ml. of water at 25 degrees Celsius under continuous stirring for five minutes. 14. A method of making a wet granulated powder formulation of diclofenac or a pharmaceutically acceptable salt thereof comprising: d) wet granulating in ethanol an admixture of diclofenac or a pharmaceutically acceptable salt thereof, a first portion of coarse mannitol, and a bicarbonate to form a wet granulate; and e) admixing said wet granulate with a second portion of coarse mannitol and fine mannitol. 15. The method of claim 14, further comprising admixing said wet granulate with glyceryl dibehenate. 16. The method of claim 14 wherein said wet granulate further comprises: a) from about 8 to about 15 weight parts diclofenac potassium; b) from about 12 to about 20 weight parts coarse mannitol; and c) from about 3 to about 7 weight parts potassium bicarbonate. 17. The method of claim 14 wherein from about 30 to about 60 weight parts of wet granulate are admixed with: a) from about 100 to about 160 weight parts coarse mannitol; b) from about 12 to about 20 weight parts fine mannitol; and from about 0.2 to about 0.7 weight parts glyceryl dibehenate. 18. A powder sachet dosage form formulation wherein: a) said formulation comprises: i) 50 or 25 mg of diclofenac potassium per 900 mg of said formulation; ii) from 50 to 100 mg. of fine mannitol per 900 mg. of said formulation; and iii) from 600 to 700 mg. of coarse mannitol per 900 mg. of said formulation, wherein: b) said fine mannitol has an average particle size of between 10 and 180 micrometers, at a weight ratio of fine mannitol to diclofenac potassium in the range from 1:2 to 5:1; c) said coarse mannitol has an average particle diameter of between 75 and 300 micrometers, at a weight ratio of coarse mannitol to diclofenac in the range from 10:1 to 20:1.