Use of cannabidiol prodrugs in pharmaceutical compositions
View Patent ↗Described herein are cannabidiol prodrugs used in pharmaceutical compositions as well as microneedle drug delivery systems comprising a pharmaceutical compositions comprising pharmaceutically active agents (e.g., cannabidiol and prodrugs of cannabidiol) and microneedle arrays suitable for local and systemic delivery of the active agent to a mammal. Also described herein are methods of using a microneedle transdermal or topical drug delivery systems comprising pharmaceutical compositions, comprising cannabidiol and prodrugs of cannabidiol, and microneedle arrays in the treatment disease, including pancreatitis and pancreatic cancer.
1. A microneedle drug delivery system for transdermal or topical administration of a cannabidiol prodrug to a mammal comprising:
(a) a pharmaceutical composition in the form of a hydrogel comprising
(i) about 0.1% to about 40% of a cannabidiol prodrug:
where X − is a counter ion derived from pharmaceutically acceptable acids,
(ii) about 0.1% to about 20% of one or more co-solvents;
(iii) about 15% to about 95% a lower alcohol; and
(iv) water in a quantity sufficient for the composition to total 100% (wt/wt);
(b) a microneedle array; and
(c) a matrix- or reservoir-type patch incorporating at least the pharmaceutical composition and the microneedle array.
2. The drug delivery system pharmaceutical composition of claim 1 , wherein the cannabidiol prodrug is present in an amount of about 5% to about 30% (wt/wt) of the pharmaceutical composition.
3. The drug delivery system pharmaceutical composition of claim 1 , wherein the cannabidiol prodrug is present in an amount of about 10% to about 20% (wt/wt) of the pharmaceutical composition.
4. The drug delivery system pharmaceutical composition of claim 1 , further comprising about 0.1% to about 20% of one or more cosolvents; about 15% to about 95% a lower alcohol; and water in a quantity sufficient for the composition to total to 100% (wt/wt), wherein each of the one or more co-solvents is selected from the group consisting of: ethanol, benzyl alcohol, and mixtures of the foregoing.
5. The drug delivery system of claim 1 , wherein the pharmaceutical composition further comprises a COX inhibitor selected from the group consisting of: a non-specific COX inhibitor, a COX-1 inhibitor and a COX-2 inhibitor.
6. The dnig delivery system claim 5 , wherein the non-specific COX inhibitor comprises at least one of: aspirin, diclofenac, diflunisal, fenoprofen, flurbiprofen, ibuprofen, indomethacin, ketoprofen, ketorolac, mefenamic acid, meloxicam, nabumetone, naproxen, olsalzine, oxaprozin, piroxicam, salsalate, sulfasalazine, sulindac and tolmetin.
7. The drug delivery system of claim 5 , wherein the COX-1 inhibitor comprises at least one of: mofezolac, SC-560 and FR 122047.
8. The drug delivery system of claim 5 , wherein the COX-2 inhibitor comprises at least one of: etodolac, celecoxib, rofecoxib, valdecoxib, parecoxib, lumiracoxib and etoricoxib.
9. The drug delivery system of claim 1 , wherein the pharmaceutical composition further comprises an antioxidant, wherein the antioxidant comprises at least one of citric acid, butylated hydroxytoluene, ascorbic acid, glutathione, retinol, α-tocopherol, β-carotene, α-carotene, ubiquinone, butylated hydroxyanisole, ethylenediaminetetraacetic acid, selenium, zinc, lignan, uric acid, lipoic acid, and N-acetylcysteine.
10. The drug delivery system of claim 1 , wherein the pharmaceutical composition further comprises a penetration enhancer, wherein the penetration enhancer comprises at least one of: isostearic acid, octanoic acid, oleic acid, oleyl alcohol, lauryl alcohol, ethyl oleate, isopropyl myristate, butyl stearate, methyl laurate, diisopropyl adipate, glyceryl monolaurate, tetrahydrofurfuryl alcohol polyethylene glycol ether, polyethylene glycol, propylene glycol, 2-(2-ethoxyethoxy)ethanol, diethylene glycol monomethyl ether, alkylaryl ethers of polyethylene oxide, polyethylene oxide monomethyl ethers, polyethylene oxide dimethyl ethers, dimethyl sulfoxide, glycerol, acetoacetic ester, N-alkylpyrrolidone, terpenes, n-octanol, sodium oleate, D-limonene, monoolein, cineol, oleyl oleate, ethanol, propanol, butanol, 2-butanol, pentanol, 2-pentanol, hexanol, octanol, nonanol, decanol, benzyl alcohol, Polyxamer 231, Polyxamer 182, Polyxamer 184, Polysorbate 20, Polysorbate 60, Brij 30, Brij 93, Brij 96, Brij 99, Span 20, Span 40, Span 60, Span 80, Span 85, Tween 20, Tween 40, Tween 60, Tween 80, Myrj 45, Myrj 51, Myrj 52, and Miglyol 840.
11. The drug delivery system of claim 10 , wherein the penetration enhancer is present in an amount of about 0.1% to about 40% (wt/wt) of the pharmaceutical composition.
12. The drug delivery system of claim 10 , wherein the penetration enhancer is present in an amount of about 0.1% to about 30% (wt/wt) of the pharmaceutical composition.
13. The drug delivery system of claim 10 , wherein the penetration enhancer is present in an amount of about 1% to about 20% (wt/wt) of the pharmaceutical composition.
14. The drug delivery system of claim 10 , wherein the penetration enhancer is present in an amount of about 1% to about 10% (wt/wt) of the pharmaceutical composition.
15. The drug delivery system pharmaceutical composition of claim 1 4, wherein the lower alcohol comprises at least one of ethanol and isopropanol.
16. The drug delivery system pharmaceutical composition of claim 1 , wherein the pharmaceutical composition delivers a therapeutically effective amount of the cannabidiol prodrug over a period of time selected from the group consisting of: about 1 hour, about 2 hours, about 3 hours, about 4 hours, about 6 hours, about 12 hours, about 24 hours, about 48 hours, about 72 hours, about 96 hours, about 5 days, about 6 days or about 7 days.
17. The pharmaceutical composition of claim 1, wherein the cannabidiol prodrug is synthetic.
18. A microneedle drug delivery system for transdermal or topical administration of a cannabidiol prodrug to a mammal comprising:
(a) a pharmaceutical composition comprising a cannabidiol prodrug:
where X − is a counter ion derived from pharmaceutically acceptable acids;
(b) a microneedle array; and
(c) a matrix- or reservoir-type patch incorporating at least the pharmaceutical composition and the microneedle array.