Transdermal formulation for the treatment of pain and/or inflammation
Described herein are transdermal formulations of phytocannabinoids and methods of using the same in the treatment of pain and/or inflammation.
1. A transdermal formulation consisting of from about 0.05% w/w to about 50% w/w cannabidiol dispersed in a pharmaceutically acceptable carrier consisting of:
from about 3% w/w to about 30% w/w penetration enhancer selected from the group consisting of diethylene glycol monoethyl ether, lauryl alcohol, dimethyl sulfoxide (DMSO), dimethyl acetamide, N-methyl pyrrolidone, oleic acid, azone, urea, terpene, and combinations of any two or more thereof,
from about 0.8% w/w to about 1.3% w/w thickening agent selected from the group consisting of cross-linked polyacrylic acid polymers; hydroxyethylcellulose, ethyl cellulose, hydroxypropyl cellulose, carboxymethyl cellulose, sodium carboxymethyl cellulose; xanthan gum, locust beam gum, guar gum; alginic acid; PEMULEN™ (a copolymer of acrylic acid and C 10 -C 30 alkyl acrylate cross-linked with allyl pentaerythritol); and combinations of any two or more thereof,
from about 0.25% w/w to about 6% w/w buffering agent selected from the group consisting of triethanolamine, potassium hydroxide, cocoamidodiethylamine, and combinations of any two or more thereof,
from about 0.05% w/w to about 0.08% w/w sequestering agent selected from the group consisting of EDTA and salts and solvates thereof; citric acid; tartaric acid; and combinations of any two or more thereof,
from about 0.4% w/w to about 0.8% w/w of preservative selected from the group consisting of phenoxyethanol, ethylhexylglycerine, hydantoin, sorbic acid, anisic acid, and combinations or any two or more thereof, and
up to about 95.45% w/w of deionized water;
wherein all percentages are based on the total weight of the formulation;
wherein the transdermal formulation is a semi-solid formulation selected from the group consisting of a gel, a lotion, a cream, an ointment, a serum, and a foam.
2. The formulation of claim 1 , wherein the penetration enhancer is diethylene glycol monoethyl ether.
3. The formulation of claim 1 , wherein the thickening agent is a cross-linked polyacrylic acid polymer.
4. The formulation of claim 1 , wherein the buffering agent is triethanolamine.
5. The formulation of claim 1 , wherein the sequestering agent is selected from the group consisting of EDTA and salts and solvates thereof.
6. The formulation of claim 1 , wherein the preservative is phenoxyethanol.
7. The formulation of claim 1 , consisting of
about 0.20% w/w cannabidiol,
about 18% w/w diethylene glycol monoethyl ether,
about 1% w/w cross-linked polyacrylic acid polymer,
about 0.3% w/w triethanolamine,
about 0.5% w/w phenoxyethanol,
about 0.05% w/w disodium EDTA dihydrate, and
q.s. deionized water.
8. The formulation of claim 1 , wherein the formulation exhibits a lag effect wherein, following four consecutive hourly applications of the formulation to skin, the amount of cannabidiol delivered through the skin after 21 hours is greater than the amount delivered through the skin after 5 hours, as assessed in an in vitro permeation study using human cadaver skin.
9. A method of treating musculoskeletal pain and/or inflammation in a subject in need thereof, the method comprising topically administering to one or more regions of skin on the subject a therapeutically effective amount of a transdermal formulation of claim claim 1 .
10. The method of claim 9 , wherein the transdermal formulation is administered by topical application to the region of skin on the subject without microneedle delivery.
11. The method of claim 9 , wherein the transdermal formulation is administered once every hour for an initial period of three hours for a total of four applications and then subsequently administered 3-4 times per day.
12. The method of claim 9 , wherein the musculoskeletal pain and/or inflammation is located at one or more of the foot, ankle, knee, hip, hand, wrist, elbow, neck, scalp, back, chest, abdomen, shoulder, arm, or leg, of the subject.
13. A method for relieving pain associated with osteoarthritis of one or more joints in a subject in need thereof, the method comprising topically administering a therapeutically effective amount of a transdermal formulation of claim 1 to one or more regions of skin covering the one or more joints on the subject.
14. The method of claim 13 , wherein the one or more joints are located at one or more of the foot, ankle, knee, hip, hand, wrist, elbow, neck, back, or shoulder of the subject.
15. The method of claim 13 , wherein the transdermal formulation is administered by topical application to the region of skin on the subject without microneedle delivery.
16. The method of claim 13 , wherein the transdermal formulation is administered once every hour for an initial period of three hours for a total of four applications and then subsequently administered 3-4 times per day.
17. A container, comprising:
the transdermal formulation of claim 1 , and
a medical grade pump dispenser to dispense the transdermal formulation.
18. The container of claim 17 , wherein the medical grade pump dispenser comprises a cooling tip.
19. The container of claim 17 , wherein the formulation consists of:
about 0.20% w/w cannabidiol,
about 18% w/w diethylene glycol monoethyl ether,
about 1% w/w cross-linked polyacrylic acid polymer,
about 0.3% w/w triethanolamine,
about 0.5% w/w phenoxyethanol,
about 0.05% w/w disodium EDTA dihydrate, and
q.s. deionized water.