Ibuprofen for Topical Administration

Abstract

Set forth herein is a preparation of ibuprofen (2-(4-isobutylphenyl)propionic acid) in the free acid form that is suitable for topical administration. The topical ibuprofen formulation is prepared by dissolving the free acid form of ibuprofen, or preparing a homogeneous suspension of the free acid form of ibuprofen, in the presence of a pharmaceutically acceptable solvent so as to produce a topical drug formulation compatible with the penetration of 2-(4-isobutylphenyl) propionic acid through the skin tissue. Topical formulations of ibuprofen can be based on a pharmaceutically acceptable solvent such as, e.g., a pyrrolidone solvent or dimethylacetamide.

1 . A composition comprising:
 a) the free acid form of 2-(4-isobutylphenyl)propionic acid;   b) a pharmaceutically acceptable solvent; and   c) at least one excipient.   
   
   
       2 . The composition of  claim 1 , wherein the 2-(4-isobutylphenyl)propionic acid has a half life in the composition of at least six months at twenty-five degrees Celsius. 
   
   
       3 . The composition of  claim 1 , wherein the solvent is a pyrrolidone solvent. 
   
   
       4 . The composition of  claim 3 , wherein the solvent is selected from the group consisting of N-methyl-2-pyrrolidone and 2-pyrrolidone. 
   
   
       5 . The composition of  claim 1 , wherein the solvent is dimethylacetamide. 
   
   
       6 . The composition of  claim 1 , wherein the 2-(4-isobutylphenyl)propionic acid is dissolved in the solvent. 
   
   
       7 . The composition of  claim 1 , wherein the 2-(4-isobutylphenyl)propionic acid is suspended in a particulate form in the solvent. 
   
   
       8 . The composition of  claim 7 , wherein the 2-(4-isobutylphenyl)propionic acid is in a nanoparticulate form in the solvent. 
   
   
       9 . The composition of  claim 1 , wherein the at least one excipient includes water. 
   
   
       10 . The composition of  claim 1 , wherein the at least one excipient includes a water-soluble excipient and a water-insoluble excipient. 
   
   
       11 . The composition of  claim 10 , further comprising an emulsifier. 
   
   
       12 . The composition of  claim 1 , wherein the 2-(4-isobutylphenyl)propionic acid is in a protonated form. 
   
   
       13 . The composition of  claim 1 , wherein the excipient further comprises a buffer, the buffer having at least one acid ionization constant (pKa) chosen so as to maintain the 2-(4-isobutylphenyl)propionic acid in a protonated form. 
   
   
       14 . The composition of  claim 13 , wherein the buffer has an acid ionization constant (pKa) of less than 7. 
   
   
       15 . A method for treating inflammation in a patient in need of therapy, comprising applying to the skin of the patient a topical formulation that comprises the composition of  claim 1 . 
   
   
       16 . A method of preparing the composition of  claim 1 , comprising preparing a solution of 2-(4-isobutylphenyl)propionic acid in a pharmaceutically acceptable solvent and combining said solution with an excipient that is suitable for topical application. 
   
   
       17 . The method of  claim 16 , wherein said solution preparation comprises dissolving said 2-(4-isobutylphenyl)propionic acid in said solvent. 
   
   
       18 . The method of  claim 16 , wherein said solution preparation comprises suspending homogeneously a particulate form of said 2-(4-isobutylphenyl)propionic acid in said solvent. 
   
   
       19 . The method of  claim 16 , wherein the solvent is a pyrrolidone solvent. 
   
   
       20 . The method of  claim 19 , wherein the solvent is selected from the group consisting of N-methyl-2-pyrrolidone and 2-pyrrolidone. 
   
   
       21 . The method of  claim 16 , wherein the organic solvent is dimethylacetamide (DMA). 
   
   
       22 . A method of preparing an a pharmacological composition the method comprising:
 a) solubilizing ibuprofen in a pharmaceutically acceptable solvent;   b) creating an active drug containing solution by combining the solubilized ibuprofen with a skin conditioner and a preservative;   c) creating an aqueous solution containing a conditioner, a pH stabilizer and a preservative;   d) creating an emollient phase by combining an emulsifier, a preservative, an oil and a stabilizer;   e) combining and homogenizing the emollient phase and the aqueous solution to create a homogenized mixture; and   f) adding the active drug containing solution to the homogenized mixture under temperature conditions avoiding degradation of the ibuprofen.   
   
   
       23 . The method of  claim 15 , wherein the solvent is a pyrrolidone solvent. 
   
   
       24 . The method of  claim 16 , wherein the solvent is selected from the group consisting of N-methyl-2-pyrrolidone and 2-pyrrolidone. 
   
   
       25 . The method of  claim 15 , wherein the organic solvent is dimethylacetamide (DMA). 
   
   
       26 . A method of  claim 17 , wherein the solvent is selected from the group consisting of N-methyl-2-pyrrolidone and 2-pyrrolidone. 
   
   
       27 . A method of  claim 17 , wherein at least one of the creating an aqueous mixture, the creating an emollient phase, the combining and the homogenizing include adding a first amount of heat, and a second amount of heat is removed prior to the adding the active drug containing solution so as to create the temperature conditions that avoid degradation of the ibuprofen.