Ibuprofen for Topical Administration
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.