Delivery of naproxen and other compounds

Abstract

The present invention generally relates to the transdermal delivery of various compositions. In some aspects, the transdermal delivery may be facilitated by the use of a hostile biophysical environment. One set of embodiments provides a composition for topical delivery comprising ibuprofen and/or an ibuprofen salt, a nitric oxide donor, and optionally, a hostile biophysical environment. In some cases, the composition may be stabilized using a stabilization polymer such as xanthan gum, KELTROL® BT and/or KELTROL® RD; propylene glycol; and a polysorbate surfactant such as Polysorbate 20, which unexpectedly provides temperature stability to the composition, e.g., at elevated temperatures such as at least 40° C. (at least about 104° F.), as compared to compositions lacking one or more of these.

What is claimed is: 
     
         1 - 112 . (canceled) 
     
     
         113 . A composition for topical delivery to the skin of a subject, the composition comprising:
 a nitric oxide donor comprising L-arginine and/or an L-arginine salt;   a hostile biophysical environment comprising an ionic salt;   a stabilization polymer comprising an effective amount of xanthan gum;   propylene glycol;   a polysorbate surfactant; and   naproxen and/or a naproxen salt,   wherein the composition is an emulsion, and wherein the composition is stable when exposed to a temperature of 40° C. for a time of at least about a day.   
     
     
         114 . The composition of  claim 113 , wherein the composition is stable when exposed to a temperature of 40° C. for a time selected from the group consisting of at least about a week, and at least about 4 weeks. 
     
     
         115 . The composition of  claim 113 , wherein the composition is a form selected from the group consisting of a cream, a gel, a lotion, and a transdermal patch. 
     
     
         116 . The composition of  claim 113 , wherein the nitric oxide donor is present at a concentration selected from the group consisting of at least about 0.5% by weight of the composition, at least about 5% by weight of the composition, and at least about 7% by weight of the composition. 
     
     
         117 . The composition of  claim 113 , wherein the hostile biophysical environment comprises an ionic salt present in a concentration selected from the group consisting of at least about 5% by weight of the composition, at least about 7% by weight of the composition, and at least about 10% by weight of the composition. 
     
     
         118 . The composition of  claim 113 , wherein the hostile biophysical environment comprises one or more salts selected from the group consisting of choline chloride, magnesium chloride, and calcium chloride. 
     
     
         119 . The composition of  claim 113 , wherein the hostile biophysical environment has an ionic strength selected from the group consisting of at least about 0.25 M and at least about 1M. 
     
     
         120 . The composition of  claim 113 , wherein the hostile biophysical environment has a pH selected from the group consisting of at least about 9 and at less than about 5. 
     
     
         121 . The composition of  claim 113 , wherein the composition further comprises a package containing the nitric oxide donor, the package being selected from the group consisting of liposomes, emulsions of collagen, collagen peptides and combinations thereof. 
     
     
         122 . The composition of  claim 113 , wherein the stabilization polymer is present in a concentration selected from the group consisting of at least about 0.5% by weight of the composition and at least about 0.8% by weight of the composition. 
     
     
         123 . The composition of  claim 113 , wherein the propylene glycol is present in a concentration selected from the group consisting of at least about 3% by weight of the composition and at least about 5% by weight of the composition. 
     
     
         124 . The composition of  claim 113 , wherein the polysorbate surfactant is present in a concentration selected from the group consisting of at least about 1% by weight of the composition and at least about 2% by weight of the composition. 
     
     
         125 . The composition of  claim 113 , wherein the naproxen and/or the naproxen salt is present at a concentration selected from the group consisting of at least about 1% by weight of the composition, at least about 3% by weight of the composition, at least about 5% by weight of the composition, and at least about 7% by weight of the composition. 
     
     
         126 . The composition of  claim 113 , wherein the composition further comprises one or more of glyceryl stearate, cetyl alcohol, squalene, isopropyl myristate, and oleic acid. 
     
     
         127 . The composition of  claim 113 , further comprising water at a concentration selected from the group consisting of at least about 35% by weight of the composition and at least about 40% by weight of the composition. 
     
     
         128 . The composition of  claim 113 , wherein the nitric oxide donor comprises L-arginine. 
     
     
         129 . The composition of  claim 113 , wherein the nitric oxide donor comprises L-arginine hydrochloride. 
     
     
         130 . The composition of  claim 113 , wherein the composition comprises sodium chloride. 
     
     
         131 . The composition of  claim 113 , wherein the composition comprises citric acid. 
     
     
         132 . A method, comprising applying the composition of  claim 113  to a subject.