Novel formulation of diclofenac

Abstract

The present invention relates to methods for producing particles of diclofenac using dry milling processes as well as compositions comprising diclofenac, medicaments produced using diclofenac in particulate form and/or compositions, and to methods of treatment of an animal, including man, using a therapeutically effective amount of diclofenac administered by way of said medicaments

1 .- 41 . (canceled) 
     
     
         42 . A method for preparing a solid oral unit dose of a pharmaceutical composition containing 18 mg of diclofenac acid, wherein the D(90) of the diclofenac acid, on a particle volume basis, is less than 5000 nm, and wherein the unit dose, when tested in vitro by USP Apparatus I (Basket) method of U.S. Pharmacopoeia at 100 rpm at 37° C. in 900 ml of 0.05% sodium lauryl sulfate in citric acid solution buffered to pH 5.75, has a dissolution rate of diclofenac acid such that 94%, by weight, is released by 75 minutes, the method comprising:
 a) milling a composition comprising diclofenac acid to prepare particles of diclofenac acid having a D(90) of the diclofenac acid, on a particle volume basis, that is less than 5000 nm; 
 b) combining the particles of diclofenac acid with one or more pharmaceutically acceptable excipients to prepare pharmaceutical composition; and 
 c) preparing solid unit dosage forms of the pharmaceutical composition comprising 18 mg of diclofenac acid. 
 
     
     
         43 . The unit dose of  claim 42 , wherein the D(90) of the diclofenac acid, on a particle volume basis, is less than 3000 nm. 
     
     
         44 . The unit dose of  claim 42 , wherein the unit dose has a dissolution rate of diclofenac acid such that 94%, by weight, is released by 60 minutes. 
     
     
         45 . The unit dose of  claim 42 , wherein the unit dose has a dissolution rate of diclofenac acid such that 94%, by weight, is released by 45 minutes. 
     
     
         46 . The unit dose of  claim 42 , wherein the unit dose has a dissolution rate of diclofenac acid such that 94%, by weight, is released by 30 minutes. 
     
     
         47 . The unit dose of  claim 42 , wherein the D(90) of the diclofenac acid, on a particle volume basis, is less than 2000 nm. 
     
     
         48 . The unit dose of  claim 42 , wherein the unit dose has a dissolution rate of diclofenac acid such that 94%, by weight, is released by 60 minutes. 
     
     
         49 . The unit dose of  claim 42 , wherein the unit dose has a dissolution rate of diclofenac acid such that 94%, by weight, is released by 45 minutes. 
     
     
         50 . The unit dose of  claim 42 , wherein the unit dose has a dissolution rate of diclofenac acid such that 94%, by weight, is released by 30 minutes. 
     
     
         51 . The unit dose of  claim 42 , wherein the D(90) of the diclofenac acid, on a particle volume basis, is less than 1900 nm. 
     
     
         52 . The unit dose of  claim 42 , wherein the D(90) of the diclofenac acid, on a particle volume basis, is less than 1800 nm. 
     
     
         53 . The unit dose of  claim 42 , wherein the particles of diclofenac have a median particle size on particle volume basis between 1000 nm and 25 nm. 
     
     
         54 . The unit dose of  claim 42 , wherein the one or more pharmaceutically acceptable carriers comprises lactose. 
     
     
         55 . A method for preparing solid oral unit dose of a pharmaceutical composition containing 35 mg of diclofenac acid, wherein the D(90) of the diclofenac acid, on a particle volume basis, is less than 5000 nm, and wherein the unit dose, when tested in vitro by USP Apparatus I (Basket) method of U.S. Pharmacopoeia at 100 rpm at 37° C. in 900 ml of 0.05% sodium lauryl sulfate in citric acid solution buffered to pH 5.75, has a dissolution rate of diclofenac acid such that 95%, by weight, is released by 75 minutes, the method comprising:
 a) milling a composition comprising diclofenac acid to prepare particles of diclofenac acid having a D(90) of the diclofenac acid, on a particle volume basis, that is less than 5000 nm; 
 b) combining the particles of diclofenac acid with one or more pharmaceutically acceptable excipients to prepare pharmaceutical composition; and 
 c) preparing solid unit dosage forms of the pharmaceutical composition comprising 35 mg of diclofenac acid. 
 
     
     
         56 . The unit dose of  claim 55 , wherein the D(90) of the diclofenac acid, on a particle volume basis, is less than 3000 nm. 
     
     
         57 . The unit dose of  claim 55 , wherein the unit dose has a dissolution rate of diclofenac acid such that 95%, by weight, is released by 60 minutes. 
     
     
         58 . The unit dose of  claim 55 , wherein the unit dose has a dissolution rate of diclofenac acid such that 95%, by weight, is released by 45 minutes. 
     
     
         59 . The unit dose of  claim 55 , wherein the unit dose has a dissolution rate of diclofenac acid such that 95%, by weight, is released by 30 minutes. 
     
     
         60 . The unit dose of  claim 55 , wherein the D(90) of the diclofenac acid, on a particle volume basis, is less than 2000 nm. 
     
     
         61 . The unit dose of  claim 55 , wherein the unit dose has a dissolution rate of diclofenac acid such that 95%, by weight, is released by 60 minutes. 
     
     
         62 . The unit dose of  claim 55 , wherein the unit dose has a dissolution rate of diclofenac acid such that 95%, by weight, is released by 45 minutes. 
     
     
         63 . The unit dose of  claim 55 , wherein the unit dose has a dissolution rate of diclofenac acid such that 95%, by weight, is released by 30 minutes. 
     
     
         64 . The unit dose of  claim 55 , wherein the D(90) of the diclofenac acid, on a particle volume basis, is less than 1900 nm. 
     
     
         65 . The unit dose of  claim 55 , wherein the D(90) of the diclofenac acid, on a particle volume basis, is less than 1800 nm. 
     
     
         66 . The unit dose of  claim 55 , wherein the particles of diclofenac have a median particle size on particle volume basis between 1000 nm and 25 nm.