Transdermal formulation for delivery of hydrophobic compounds and process for the preparation thereof

A transdermal emulsion formulation comprising:

• (a) an aqueous phase comprising water and at least one emulsion stabilizer selected from natural polymers, gums and synthetic polymers, and mixtures thereof;
• wherein the natural polymers are selected from alginic acid, cellulose, and scleroglucans, and mixtures thereof, wherein the gums are selected from xanthan gum, tara gum, guar gum and arabic gum, and mixtures thereof, and wherein the synthetic polymers are selected from polyacrylates, polyisobutenes and polysorbates, and mixtures thereof, and wherein the at least one emulsion stabilizer in the aqueous phase is present in an amount of about 0.1 wt % to about 1 wt %;
• (b) an oil phase comprising:
• at least one emulsifier selected from oil-soluble fatty acid esters or mixtures of fatty acid esters in which the fatty acid esters have a fatty acid composition similar to the fatty acid composition of skin, wherein the oil-soluble fatty acid esters or mixture of fatty acid esters are C14-C26-fatty acids esterified with a fatty acid alcohol selected from cetyl alcohol, cetaryl alcohol, lauryl alcohol, stearyl alcohol, myristyl alcohol and oleyl alcohol or with a sugar alcohol selected from sorbitol, glycerol, mannitol, inositol, xylitol, erythritol, threitol, arabitol, ribitol, or mixtures thereof, wherein the at least one emulsifier in the oil phase is present in an amount of about 2 wt % to about 8 wt %;
• at least one emulsion stabilizer selected from one or more waxes, wherein the at least one emulsion stabilizer in the oil phase is present in an amount of about 1 wt % to about 10 wt %;
• at least one emollient comprising at least one flavonoid, wherein the at least one emollient is a natural oil or extract from citrus, Ginkgo biloba, tea, wine, cacao, onion, kale, parsley, red beans, broccoli, endive, celery, cranberries, blackberries, red raspberries, blackcurrants, acai, blueberries, bilberries, milk thistle, apples, hawthorn, Echinacea, grapes, and/or soy, or wherein the at least one emollient comprising at least one flavonoid in the oil phase is a natural oil or extract from the genera Rubus, Ribes, Argania, Nymphaea, Peucedanum or Imperatoria, Sambucus, Calendula, Butea, Citrus (e.g. lime), or species or subspecies thereof, and wherein the at least one emollient comprising at least one flavonoid in the oil phase is present in an amount of about 3 wt % to about 15 wt %;
• at least one other emollient selected from octyl palmitate, isopropyl stearate, isopropyl palmitate, octyl dodecanol, or mixtures thereof, wherein the at least one other emollient in the oil phase is present in an amount of about 1 wt % to about 10 wt %;
• and
• a terpene-rich natural butter, which is a terpene-rich seed butter, wherein the terpene-rich natural butter in the oil phase is present in an amount of about 1 wt % to about 10 wt %;
• wherein the oil and aqueous phase form an emulsion;
• (c) an external phase comprising:
• at least one terpene-rich extract or oil selected from essential oils or extracts from fruits vegetables, herbs, spices, legumes, leaves, seeds, or mixtures thereof, wherein the at least one terpene-rich extract or oil is present in an amount of about 0.1 wt % to about 10 wt %;
• at least one penetration enhancers selected from a glycol, dimethyl isosorbide, or a mixture of glycols and/or dimethylisosorbide, wherein the at least one penetration enhancer is present in an amount of about 1 wt % to about 5 wt %;
• a phospholipid-complexed flavonoid, wherein the phospholipid is selected from phosphatidylcholine, phosphatidylethanolamine, phosphatidylinostinol, phosphatidylserine, or mixtures thereof, and wherein the flavonoid is selected from quercetin, myrcetin, apigenin, rutin, or mixtures thereof, wherein the phospholipid- complexed flavonoid is present in an amount of about 1 wt % to about 4 wt %;
• and
• a hydrophobic active agent, wherein the hydrophobic active agent comprises:
• nabilone present in an amount of about 0.01 wt % to about 1 wt %;
• buprenorphine present in an amount of about 0.001 wt % to about 1 wt %;
• bupivacaine present as hydrochloride in an amount of about 0.1 wt % to about 5 wt %;
• lidocaine present in an amount of about 0.1 wt % to about 10 wt %;
• a combination of bupivacaine, lidocaine and epinephrine, wherein the bupivacaine is present as hydrochloride in an amount of about 0.1 wt % to about 5 wt %, the lidocaine is present in an amount of about 0.1 wt % to about 10 wt %, and the epinephrine is present in an amount of about 0.001 wt % to about 1 wt %;
• a synthetic cannabinoid present in an amount of about 0.1 wt % to about 5 wt %.
• one or more plant-derived cannabinoids, each present in an amount of about 0.1 wt % to about 5 wt %, optionally wherein the one or more plant-derived cannabinoid is THC, CBD, or a combination of THC and CBD;
• and
• optionally,
• (d) at least one preservative phase.