Method of preparing nanoparticles by hot-melt extrusion
View Patent ↗The present invention provides a nanoparticle dispersion for topical delivery to skin of a mammal. The nanoparticle dispersion includes: one or more hydrophobic bioactive agents or one or more hydrophobic drugs; one or more surfactants; one or more water immiscible oils; and water. Methods of preparing nanoparticles dispersions by hot melt extrusion are also provided.
1. A nanoparticle dispersion comprising;
from 0.5 wt. % to 8.5% of one or more hydrophobic drugs and/or hydrophobic bioactive agents;
from 1.6 wt. % to 11.9 wt. % of one or more high hydrophile-lipophile-balance (HLB) surfactants;
from 2.6 wt. % to 12.0 wt. % of one or more low hydrophile-lipophile-balance (HLB) surfactants;
from 13.9 wt. % to 41.8 wt. % of one or more water immiscible oils; and
from 39.1 wt. % to 58.1 wt. % water, wherein:
the dispersion is without lamellar structure; and
the dispersion has a latent lamellar structure.
2. The nanoparticle dispersion of claim 1 , wherein the one or more high hydrophile-lipophile-balance (HLB) surfactants comprises:
an ester type polyethoxylated selected from the group consisting of PEG100 stearate, PEG20 stearate, PEG30 glyceryl cocoate, PEG32 stearate, polysorbate 20, and polysorbate 80; and
a phospholipid low hydrophile-lipophile-balance (HLB) surfactants selected from the group consisting of phosphatidylcholine and lecithin.
3. The nanoparticle dispersion of claim 1 , wherein the one or more high hydrophile-lipophile-balance (HLB) surfactants comprises one or more ether type polyethoxylated high hydrophile-lipophile-balance (HLB) surfactants selected from the group consisting of laureth-23, laureth-30, steareth-100, steareth-20, steareth-40, ceteareth-20, and ceteareth-30.
4. The nanoparticle dispersion of claim 3 , further comprising one or more ester type polyethoxylated high hydrophile-lipophile-balance (HLB) surfactants selected from the group consisting of PEG100 stearate, PEG20 stearate, PEG30 glyceryl cocoate; PEG32 stearate; and polysorbate 20.
5. The nanoparticle dispersion of claim 4 , wherein a weight ratio of the ether type polyethoxylated high hydrophile-lipophile-balance HLB surfactant to the ester type polyethoxylated high hydrophile-lipophile-balance HLB surfactant is greater than 1:1.
6. The nanoparticle dispersion of claim 3 , further comprising one or more non-polyethoxylated high hydrophile-lipophile-balance (HLB) surfactants selected from the group consisting of cocoglucoside, decyl glucoside, and xylityl caprate/caprylate.
7. The nanoparticle dispersion of claim 1 , comprising a hydrophobic drug selected from the group consisting of aspirin, atropine, benzocaine, cortisol, cortisone, diclofenac, diflunisal, dronabinol, estradiol, flurbiprofen, haloperidol, hydrocortisone, ibuprofen, S-ibuprofen, ketoprofen, ketorolac, lidocaine, minoxidil, naproxen, nicotine, penicillin V, prednisone, progesterone, salicylic acid, and sulindac.
8. The nanoparticle dispersion of claim 7 , wherein the hydrophobic drug is aspirin, benzocaine, hydrocortisone, diclofenac and lidocaine.
9. The nanoparticle dispersion of claim 1 comprising a hydrophobic bioactive agent selected from the group consisting of an oil soluble vitamin or provitamin, an essential oil, a terpenoid, a diterpenoid, a polyterpenoid, a cannabinoid, a polyphenol compound, and a fatty acid.
10. The nanoparticle dispersion of claim 9 , wherein the hydrophobic bioactive agent is a vitamin or provitamin selected from the group consisting of retinal, retinyl palmitate, retinyl sunflowerate, ascorbyl palmitate, tetrahexyldecyl ascorbate, cholecalciferol, ergocalciferol, tocopherol, tocopheryl acetate, phylloquinone, and coenzyme Q.
11. The nanoparticle dispersion of claim 9 , wherein the hydrophobic bioactive agent is an essential oil selected from the group consisting of frankincense essential oil, lavender essential oil, raspberry seed oil, cranberry seed oil, tomato seed oil, black cumin seed oil, hemp flower extract, hemp seed oil, tea tree essential oil, peppermint essential oil, lemongrass essential oil, eucalyptus essential oil, rosemary essential oil, cedarwood essential oil, clove essential oil, bergamot essential oil, arnica flower essential oil, omega-3 algae oil, blackberry seed oil, broccoli seed oil, carrot seed oil, cucumber seed oil, flaxseed oil, grape seed oil, pumpkin seed oil, pomegranate seed oil, and camphor essential oil.
12. The nanoparticle dispersion of claim 9 , wherein the hydrophobic bioactive agent is a terpenoid or derivative thereof selected from the group consisting of methyl salicylate, birch bark extract, geraniol, limonene, camphor, and menthol.
13. The nanoparticle dispersion of claim 9 , wherein the hydrophobic bioactive agent is a cannabinoid selected from the group consisting of cannabidiol and tetrahydrocannabinol.
14. The nanoparticle dispersion of claim 9 , wherein the hydrophobic bioactive agent is a polyphenol compound selected from the group consisting of resveratrol, ellagic acid, and tannic acid.
15. The nanoparticle dispersion of claim 9 , wherein the hydrophobic bioactive agent is a bioactive fatty acid selected from the group consisting of ricinoleic acid and undecylenic acid.
16. The nanoparticle dispersion of claim 1 , wherein the hydrophobic bioactive agent is selected from the group consisting of cannabidiol, methyl salicylate, tocopheryl acetate, ascorbyl palmitate, birch bark extract, retinyl palmitate, frankincense essential oil, omega-3 algae oil, resveratrol, undecylenic acid, coenzyme Q, and Youth Garden oil blend.
17. The nanoparticle dispersion of claim 1 , further comprising a polysaccharide selected from the group consisting of maltodextrin, cyclodextrin, hyaluronic acid, xanthan gum, and guar gum.
18. The nanoparticle dispersion of claim 1 , wherein the latent lamellar structure is characterized by the nanoparticle dispersion adopting a lamellar structure upon heating to a temperature in a range from 40° C., to 95° C.
19. The nanoparticle dispersion of claim 1 , wherein the latent lamellar structure is characterized by the dispersion exhibiting a positive peak between about 45° C., and 80° C., in the first derivative plot of normalized conductivity versus temperature, the positive peak having a peak amplitude greater than about 0.1° C. −1 .
20. The nanoparticle dispersion of claim 1 , wherein the latent lamellar structure is characterized by the dispersion exhibiting an optical birefringence when observing the dispersion through cross polarized films upon heating to temperatures in a range from 60° C., to 95° C.
21. The nanoparticle dispersion of claim 1 , wherein the one or more hydrophobic drugs and/or hydrophobic bioactive agents do not form crystals from the nanoparticle dispersion for greater than about 8 months at a temperature from about 18° C., to about 22° C.
22. The nanoparticle dispersion of claim 1 , wherein the dispersion is free of ibuprofen and S-ibuprofen.