USE OF CANNABIDIOL PRODRUGS IN TOPICAL AND TRANSDERMAL ADMINISTRATION WITH MICRONEEDLES

• US 20110052694A1
• Filed: 08/31/2010
• Published: 03/03/2011
• Est. Priority Date: 08/31/2009
• Status: Abandoned Application

• Current Assignee: Zynerba Pharmaceuticals, Inc.
• Original Assignee: AllTranz Inc.
• Inventors: Hammell, Dana Carmel, Banks, Stan Lee, Howard, Jeffery Lynn, Stinchcomb, Audra Lynn, Golinski, Miroslaw Jerzy
• Application Number:
  US12/873,248
• Publication Number:
  US 20110052694A1
• Time in Patent Office: Days
• US Class Current: 424/484
• CPC Class Codes: A61K 31/222 with compounds having aromatic groups, e.g. dipivefrine, ibopamine
• CPC Class Codes: A61K 31/225 Polycarboxylic acids
• CPC Class Codes: A61K 31/265 of carbonic, thiocarbonic, or thiocarboxylic acids, e.g. thioacetic acid, xanthogenic acid, trithiocarbonic acid
• CPC Class Codes: A61K 31/27 of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61K 9/0021 Intradermal administration, e.g. through microneedle arrays, needleless injectors mechanical aspects A61M
• CPC Class Codes: A61K 9/7007 Drug-containing films, membranes or sheets A61K9/0041, A61K9/0043, A61K9/006, A61K9/0063 take precedence
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/08 for nausea, cinetosis or vertigo; Antiemetics
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 17/04 Antipruritics
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 17/14 for baldness or alopecia
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/08 : Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 25/18 : Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/00 : Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 31/18 : for HIV
• CPC Class Codes: A61P 31/22 : for herpes viruses
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 37/02 : Immunomodulators
• CPC Class Codes: A61P 39/06 : Free radical scavengers or antioxidants
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07C 219/04 : the carbon skeleton being acyclic and saturated
• CPC Class Codes: C07C 219/16 : having at least one of the hydroxy groups esterified by an inorganic acid or a derivative thereof
• CPC Class Codes: C07C 229/12 : to carbon atoms of acyclic carbon skeletons
• CPC Class Codes: C07C 229/16 : to carbon atoms of hydrocarbon radicals substituted by amino or carboxyl groups, e.g. ethylenediamine-tetra-acetic acid, iminodiacetic acids
• CPC Class Codes: C07C 2601/16 : the ring being unsaturated
• CPC Class Codes: C07C 271/52 : to carbon atoms of hydrocarbon radicals substituted by nitrogen atoms not being part of nitro or nitroso groups

Abstract

Described herein are 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.

Claims

1. 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 having the formula;

2. The drug delivery system of claim 1, wherein the cannabidiol prodrug is selected from the group consisting of:

3. The drug delivery system of claim 1, wherein the cannabidiol prodrug selected from the group consisting of:

4. The drug delivery system of claim 1, wherein the cannabidiol prodrug is present in an amount of about 0.1% to about 50% (wt/wt) of the pharmaceutical composition.

5. The drug delivery system of claim 1, wherein the cannabidiol prodrug is present in an amount of about 0.1% to about 40% (wt/wt) of the pharmaceutical composition.

6. The drug delivery system of claim 1, wherein the cannabidiol prodrug is present in an amount of about 5% to about 30% (wt/wt) of the pharmaceutical composition.

7. The drug delivery system of claim 1, wherein the cannabidiol prodrug is present in an amount of about 10% to about 20% (wt/wt) of the pharmaceutical composition.

8. The drug delivery system of claim 1, wherein the pharmaceutical composition is in a form of a hydrogel.

9. The drug delivery system of claim 8, wherein the hydrogel is incorporated into a matrix- or reservoir-type patch.

10. 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.

11. The drug delivery system of claim 9, wherein the non-specific COX inhibitor is selected from the group consisting of:

aspirin, diclofenac, diflunisal, fenoprofen, flurbiprofen, ibuprofen, indomethacin, ketoprofen, ketorolac, mefenamic acid, meloxicam, nabumetone, naproxen, olsalzine, oxaprozin, piroxicam, salsalate, sulfasalazine, sulindac and tolmetin.

12. The drug delivery system of claim 9, wherein the COX-1 inhibitor is selected from the group consisting of:

mofezolac, SC-560 and FR122047.

13. The drug delivery system of claim 9, wherein the COX-2 inhibitor is selected from the group consisting of:

etodolac, celecoxib, rofecoxib, valdecoxib, parecoxib, lumiracoxib and etoricoxib.

14. The drug delivery system of claim 1, wherein the pharmaceutical composition further comprises is an antioxidant selected from the group consisting 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.

15. The drug delivery system of claim 1, wherein the pharmaceutical composition further comprises a penetration enhancer selected from the group consisting 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.

16. The drug delivery system of claim 15, wherein the penetration enhancer is present in an amount of about 0.1% to about 40% (wt/wt) of the pharmaceutical composition.

17. The drug delivery system of claim 15, wherein the penetration enhancer is present in an amount of about 0.1% to about 30% (wt/wt) of the pharmaceutical composition.

18. The drug delivery system of claim 15, wherein the penetration enhancer is present in an amount of about 1% to about 20% (wt/wt) of the pharmaceutical composition.

19. The drug delivery system of claim 15, wherein the penetration enhancer is present in an amount of about 1% to about 10% (wt/wt) of the pharmaceutical composition.

20. The drug delivery system of claim 1, wherein the pharmaceutical composition further comprises a lower alcohol selected from the group consisting of:

ethanol and isopropanol.

21. The drug delivery system 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.

22. A method of treating a disease state in a mammal in need thereof, comprising the step of:

(a) applying a microneedle drug delivery system as described in any of claims 1 to 20;

wherein the disease state is selected from the group consisting of;

acute pancreatitis, chronic pancreatitis, pancreatic cancer, nausea, emesis, pain, wasting syndrome, HIV-wasting, chemotherapy induced nausea and vomiting, alcohol use disorders, dystonia, multiple sclerosis, inflammatory bowel disorders, arthritis, dermatitis, Rheumatoid arthritis, systemic lupus erythematosus, melanoma, anti-inflammatory, anti-convulsant, anti-psychotic, antioxidant, neuroprotective, anti-cancer, immunomodulatory effects, peripheral neuropathic pain, neuropathic pain associated with post-herpetic neuralgia, diabetic neuropathy, shingles, burns, actinic keratosis, oral cavity sores and ulcers, post-episiotomy pain, psoriasis, pruritis, contact dermatitis, eczema, bullous dermatitis herpetiformis, exfoliative dermatitis, mycosis fungoides, pemphigus, severe erythema multiforme (e.g., Stevens-Johnson syndrome), seborrheic dermatitis, ankylosing spondylitis, psoriatic arthritis, Reiter'"'"'s syndrome, gout, chondrocalcinosis, joint pain secondary to dysmenorrhea, fibromyalgia, musculoskeletal pain, neuropathic-postoperative complications, polymyositis, acute nonspecific tenosynovitis, bursitis, epicondylitis, post-traumatic osteoarthritis, osteoarthritis, rheumatoid arthritis, synovitis, juvenile rheumatoid arthritis and inhibition of hair growth.

23. A microneedle drug delivery system for transdermal or topical administration of a cannabidiol prodrug to a mammal comprising:

(a) a pharmaceutical composition comprising

(i) about 0.1% to about 40% of a cannabidiol prodrug having the formula;

24. The drug delivery system of claim 23, wherein the cannabidiol prodrug is selected from the group consisting of:

25. The drug delivery system of claim 23, wherein the cannabidiol prodrug selected from the group consisting of:

26. The drug delivery system of claim 23, wherein the cannabidiol prodrug is present in an amount of about 5% to about 30% (wt/wt) of the pharmaceutical composition.

27. The drug delivery system of claim 23, wherein the cannabidiol prodrug is present in an amount of about 10% to about 20% (wt/wt) of the pharmaceutical composition.

28. The drug delivery system of claim 23, wherein the co-solvents is selected from the group consisting of:

ethanol, benzyl alcohol and mixtures of the foregoing.

29. The drug delivery system of claim 23, wherein the pharmaceutical composition is in the form of a hydrogel.

30. The drug delivery system of claim 29, wherein the hydrogel is incorporated into a matrix- or reservoir-type patch.

31. The drug delivery system of claim 23, 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.

32. A compound selected from the group consisting of: