TOPICAL APPLICATIONS OF WITHAFERIN A
This disclosure is directed to the topical/transdermal administration of the phytochemical, Withaferin A (WFA), for its wide range of pharmacological applications to include its anti-cancer, anti-obesity, anti-diabetic, anabolic effect on osteoporotic bone and its many other proteasomal inhibitory effects.
1 . A formulation for transdermal delivery of Withaferin A through the skin of a subject, comprising:
a therapeutically effective amount of Withaferin A;
a buffering agent comprising at least one carbonate salt, lysine, tris, a phosphate buffer and/or 2-imidazole-1-yl-3-ethoxycarbonylpropionic acid (IEPA), or a combination thereof in an amount between about 5-56% w/w; and
a penetrant portion in an amount between about 44 to 95% w/w.
2 . The formulation of claim 1 , wherein the penetrant portion comprises water in an amount less than about 85% w/w.
3 . The formulation of claim 1 , wherein the formulation comprises less than about 12% w/w lecithin.
4 . The formulation of claim 1 , wherein the penetrant portion further comprises a detergent portion in an amount between about 1 to 70% w/w.
5 . The formulation of claim 1 , wherein the buffering agent is in an amount between about 7.5-36% w/w of the formulation.
6 . The formulation of claim 1 , wherein the penetrant portion is in an amount between about 44-80% w/w of the formulation.
7 . The formulation of claim 1 , wherein the water is in an amount between about 15-42% w/w of the penetrant portion of the formulation.
8 . The formulation of claim 1 , wherein the penetrant portion comprises an alcohol in an amount less than 10% w/w of the formulation.
9 . The formulation of claim 7 , wherein the penetrant portion comprises lecithin organogel, an alcohol, a surfactant, and a polar solvent.
10 . The formulation of claim 1 , wherein the penetrant portion comprises a mixture of xanthan gum, lecithin, sclerotium gum, pullulan, or a combination thereof in an amount less than 5% w/w of the formulation.
11 . The formulation of claim 1 , wherein the penetrant portion comprises a mixture of caprylic triglycerides and capric triglycerides in amount less than 8% w/w of the formulation.
12 . The formulation of claim 1 , wherein the penetrant portion comprises lecithin, phosphatidylcholine, hydrogenated phosphatidylcholine, phosphatidylserine, phosphatidylethanolamine, phosphatidylinositol, one or more phosphatides, one or more Inositol phosphatides, or combinations thereof, in amount less than 12% w/w of the formulation.
13 . The formulation of claim 1 , wherein the penetrant portion comprises cetyl alcohol in amount less than 5% w/w of the formulation.
14 . The formulation of claim 1 wherein the penetrant portion comprises stearic acid in an amount less than 5% w/w of the formulation.
15 . The formulation of claim 1 , wherein the formulation comprises a gelling agent in an amount less than 5% w/w of the formulation.
16 . The formulation of claim 2 , wherein the detergent portion comprises a nonionic surfactant in an amount between about 2-25% w/w of the penetrant portion; and a polar solvent in an amount less than 5% w/w of the penetrant portion.
17 . The formulation of claim 1 , wherein the carbonate salt is sodium bicarbonate milled to a particle size less than 70 μm, wherein the sodium bicarbonate is solubilized in the formulation in an amount less than 10% w/w of the formulation.
18 . The formulation of claim 1 , further comprising tranexamic acid in an amount less than 5% w/w of the formulation.
19 . The formulation of claim 1 , further comprising a polar solvent in an amount less than 5% w/w of the formulation.
20 . The formulation of claim 1 , further comprises a humectant, an emulsifier, an emollient, or a combination thereof.
21 . The formulation of claim 1 , wherein the formulation has a pH of 7-10.5.
22 . A method for transdermal delivery of the formulation of claim 1 , through the skin of a subject.