CA2633515A1 - Compositions and methods for dermally treating pain - Google Patents

Compositions and methods for dermally treating pain Download PDF

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Publication number
CA2633515A1
CA2633515A1 CA002633515A CA2633515A CA2633515A1 CA 2633515 A1 CA2633515 A1 CA 2633515A1 CA 002633515 A CA002633515 A CA 002633515A CA 2633515 A CA2633515 A CA 2633515A CA 2633515 A1 CA2633515 A1 CA 2633515A1
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formulation
pain
solidified layer
volatile solvent
drug
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CA2633515C (en
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Jie Zhang
Sanjay Sharma
Kevin S. Warner
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ZARS Pharma Inc
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids

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  • Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Neurology (AREA)
  • Engineering & Computer Science (AREA)
  • Pain & Pain Management (AREA)
  • Biomedical Technology (AREA)
  • Rheumatology (AREA)
  • Neurosurgery (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Dermatology (AREA)
  • Epidemiology (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The present invention is drawn to solidifying formulations for dermal delivery of a drug for treating pain, such as musculoskeletal pain, inflammation, joint pain, or neuropathic pain. The formulation can include a drug selected from certain drug classes, a solvent vehicle, and a solidifying agent. The solvent vehicle can include a volatile solvent system comprising at least one volatile solvent, and a non-volatile solvent system comprising at least one non-volatile solvent, wherein the evaporation of at least some of the volatile solvent converts the formulation on the skin into a solidified layer and the non-volatile solvent system is capable of facilitating the topical delivery of the drug(s) at therapeutically effective rates over a sustained period of time.

Claims (103)

What Is Claimed Is:
1. A formulation for treating musculoskeletal or neuropathic pain, comprising:
a) a drug suitable for treating pain;
b) a solvent vehicle, comprising:
i) a volatile solvent system including at least one volatile solvent, and ii) a non-volatile solvent system including at least one non-volatile solvent, and c) a solidifying agent, wherein the formulation has a viscosity suitable for application and adhesion to a skin surface as a layer prior to evaporation of the volatile solvent system, the layer applied to the skin surface forms a solidified layer after at least partial evaporation of the volatile solvent system, and the drug continues to be dermally delivered at the therapeutically effective rate to treat musculoskeletal pain or inflammation after the volatile solvent system is at least substantially evaporated.
2. A formulation as in claim 1, wherein the non-volatile solvent system acts as a plasticizer for the solidifying agent.
3. A formulation as in claim 1, wherein the non-volatile solvent system facilitates transdermal delivery of the drug at a therapeutically effective rate over a sustained period of time.
4. A formulation as in claim 1, wherein the non-volatile solvent system is flux-enabling for the drug.
5. A formulation as in claim 1, wherein the formulation further comprises a pH modifying agent
6. A formulation as in claim 1, wherein the formulation further comprises an additional agent which is added to increase adhesion of the formulation when applied to the skin surface.
7. A formulation as in claim 9, wherein the additional agent includes at least one member selected from the group consisting of copolymers of methylvinyl ether and maleic anhydride, polyethylene glycol and polyvinyl pyrrolidone, gelatin, low molecular weight polyisobutylene rubber, copolymer of acrylsan alkyl/octylacrylamido, aliphatic resins, aromatic resins, and combinations thereof.
8. A formulation as in claim 1, wherein the volatile solvent system comprises water.
9. A formulation as in claim 1, wherein the volatile solvent system is substantially free of water.
10. A formulation as in claim 1, wherein the volatile solvent system includes at least member selected from the group consisting of ethanol, isopropyl alcohol, and combinations thereof.
11. A formulation as in claim 1, wherein the solidifying agent is present in the solidified layer at least at 20% by weight after substantially all of the volatile solvent system has evaporated.
12. A formulation as in claim 1, wherein the non-volatile solvent system is present in the solidified layer at least at 20% by weight after substantially all of the volatile solvent system has evaporated.
13. A formulation as in claim 1, wherein the volatile solvent system includes at least one solvent more volatile than water, and includes at least one member selected from the group consisting of ethanol, isopropyl alcohol, water, dimethyl ether, diethyl ether, butane, propane, isobutene, 1,1, difluoroethane, 1,1,1,2 tetrafluorethane, 1,1,1,2,3,3,3-heptafluoropropane, 1,1,1,3,3,3 hexafluoropropane, ethyl acetate, acetone, and combinations thereof.
14. A formulation as in claim 1, wherein the volatile solvent system includes at least one solvent more volatile than water, and includes at least one member selected from the group consisting of iso-amyl acetate, denatured alcohol, methanol, propanol, isobutene, pentane, hexane, chlorobutanol, turpentine, cytopentasiloxane, cyclomethicone, methyl ethyl ketone, and combinations thereof.
15. A formulation as in claim 1, wherein the non-volatile solvent system includes multiple non-volatile solvents admixed together which, along with other ingredients in the formulation, forms a formulation which solidifies onto the skin and delivers the drug at therapeutically effective rates over a sustained period of time.
16. A formulation as in claim 1, wherein the non-volatile solvent system comprises at least one solvent selected from the group consisting of glycerol, propylene glycol, isostearic acid, oleic acid, propylene glycol, trolamine, tromethamine, triacetin, sorbitan monolaurate, sorbitan monooleate, sorbitan monopalmitate, butanol, and combinations thereof.
17. A formulation as in claim 1, wherein the non-volatile solvent system includes at least one solvent selected from the group consisting of benzoic acid, butyl alcohol, dibutyl sebecate, diglycerides, dipropylene glycol, eugenol, fatty acids, isopropyl myristate, mineral oil, oleyl alcohol, vitamin E, triglycerides, sorbitan fatty acid surfactants, triethyl citrate, and combinations thereof.
18. A formulation as in claim 1, wherein the non-volatile solvent system includes at least one solvent selected from the group consisting of 1,2,6-hexanetriol, alkyltriols, alkyldiols, acetyl monoglycerides, tocopherol, alkyl dioxolanes, p-propenylanisole, anise oil, apricot oil, dimethyl isosorbide, alkyl glucoside, benzyl alcohol, bees wax, benzyl benzoate, butylene glycol, caprylic/capric triglyceride, caramel, cassia oil, castor oil, cinnamaldehyde, cinnamon oil, clove oil, coconut oil, cocoa butter, cocoglycerides, coriander oil, corn oil, coriander oil, corn syrup, cottonseed oil, cresol, cyclomethicone, diacetin, diacetylated monoglycerides, diethanolamine, dietthylene glycol monoethyl ether, diglycerides, ethylene glycol, eucalyptus oil, fat, fatty alcohols, flavors, liquid sugars, ginger extract, glycerin, high fructose corn syrup, hydrogenated castor oil, IP palmitate, lemon oil, lime oil, limonene, milk, monoacetin, monoglycerides, nutmeg oil, octyldodecanol, olive alcohol, orange oil, palm oil, peanut oil, PEG vegetable oil, peppermint oil, petrolatum, phenol, pine needle oil, polypropylene glycol, sesame oil, spearmint oil, soybean oil, vegetable oil, vegetable shortening, vinyl acetate, wax, 2-(2-(octadecyloxy)ethoxy)ethanol, benzyl benzoate, butylated hydroxyanisole, candelilla wax, carnauba wax, ceteareth-20, cetyl alcohol, polyglyceryl, dipolyhydroxy stearate, PEG-7 hydrogenated castor oil, diethyl phthalate, diethyl sebacate, dimethicone, dimethyl phthalate, PEG fatty acid esters, PEG-stearate, PEG-oleate, PEG laurate, PEG fatty acid diesters, PEG- dioleate, PEG-distearate, PEG-castor oil, glyceryl behenate, PEG glycerol fatty acid esters, PEG glyceryl laurate, PEG glyceryl stearate, PEG glyceryl oleate, hexylene glycerol, lanolin, lauric diethanolamide, lauryl lactate, lauryl sulfate, medronic acid, methacrylic acid, multisterol extract, myristyl alcohol, neutral oil, PEG-octyl phenyl ether, PEG-alkyl ethers, PEG-cetyl ether, PEG-stearyl ether, PEG-sorbitan fatty acid esters, PEG-sorbitan diisosterate, PEG-sorbitan monostearate, propylene glycol fatty acid esters, propylene glycol stearate, propylene glycol, caprylate/caprate, sodium pyrrolidone carboxylate, sorbitol, squalene, stear-o-wet, triglycerides, alkyl aryl polyether alcohols, polyoxyethylene derivatives of sorbitan-ethers, saturated polyglycolyzed C8-glycerides, N-methyl pyrrolidone, honey, polyoxyethylated glycerides, dimethyl sulfoxide, azone and related compounds, dimethylformamide, N-methyl formamaide, fatty acid esters, fatty alcohol ethers, alkyl-amides (N,N-dimethylalkylamides), N-methyl pyrrolidone related compounds, ethyl oleate, polyglycerized fatty acids, glycerol monooleate, glyceryl monomyristate, glycerol esters of fatty acids, silk amino acids, PPG-3 benzyl ether myristate, Di-PPG2 myreth 10-adipate, honeyquat, sodium pyroglutamic acid, abyssinica oil, dimethicone, macadamia nut oil, limnanthes alba seed oil, cetearyl alcohol, PEG-50 shea butter, shea butter, aloe vera juice, phenyl trimethicone, hydrolyzed wheat protein, and combinations thereof.
19. A formulation as in claim 1, wherein the solidifying agent includes at least one member selected from the group consisting of polyvinyl alcohol, esters of polyvinylmethylether/maleic anhydride copolymer, neutral copolymers of butyl methacrylate and methyl methacrylate, dimethylaminoethyl methacrylate-butyl methacrylate-methyl methacrylate copolymers, ethyl acrylate-methyl methacrylate-trimethylammonioethyl methacrylate chloride copolymers, prolamine (Zein), pregelatinized starch, ethyl cellulose, fish gelatin, gelatin, acrylates/octylacrylamide copolymers, and combinations thereof.
20. A formulation as in claim 1, wherein the solidifying agent includes at least one member selected from the group consisting of ethyl cellulose, hydroxy ethyl cellulose, hydroxy methyl cellulose, hydroxy propyl cellulose, hydroxypropyl methyl cellulose, carboxymethyl cellulose, methyl cellulose, polyether amides, corn starch, pregelatinized corn starch, polyether amides, shellac, polyvinyl pyrrolidone, polyisobutylene rubber, polyvinyl acetate phthalate, and combinations thereof.
21. A formulation as in claim 1, wherein the solidifying agents includes at least one member selected from the group consisting of ammonia methacrylate, carrageenan, cellulose acetate phthalate aqueous, carboxy polymethylene, cellulose acetate (microcrystalline), cellulose polymers, divinyl benzene styrene, ethylene vinyl acetate, silicone, guar gum, guar rosin, gluten, casein, calcium caseinate, ammonium caseinate, sodium caseinate, potassium caseinate, methyl acrylate, microcrystalline wax, polyvinyl acetate, PVP ethyl cellulose, acrylate, PEG/PVP, xantham gum, trimethyl siloxysilicate, maleic acid/anhydride colymers, polacrilin, poloxamer, polyethylene oxide, poly glactic acid/poly-I-lactic acid, turpene resin, locust bean gum, acrylic copolymers, polyurethane dispersions, dextrin, polyvinyl alcohol-polyethylene glycol co-polymers, methyacrylic acid-ethyl acrylate copolymers, methacrylic acid and methacrylate based polymers such as poly(methacrylic acid), and combinations thereof.
22. A formulation as in claim 1, wherein the drug includes multiple pharmaceutically active agents.
23. A formulation as in claim 1, wherein pain is musculoskeletal pain or inflammation and is in or around a finger joint.
24. A formulation as in claim 1, wherein the pain is musculoskeletal pain or inflammation and is in or around a wrist, elbow, or knee.
25. A formulation as in claim 1, wherein the pain is musculoskeletal pain or inflammation and is in or around a back or neck.
26. A formulation as in claim 1, wherein the pain is musculoskeletal pain or inflammation and the drug includes at least one member from a class of drugs selected from the group consisting of non-steroidal anti-inflammatory drugs (NSAIDs), COX inhibitors, local anesthetics, 5HT-2A receptor antagonists, and steroids, prodrugs thereof, and combinations thereof.
27. A formulation as in claim 1, wherein the pain is musculoskeletal pain or inflammation and the drug includes at least one member selected from the group consisting of ketoprofen, diclofenac, ketanserin, and combinations thereof.
28. A formulation as in claim 1, wherein the pain is musculoskeletal pain or inflammation and the drug includes at least one member selected from the group consisting of lidocaine, ropivacaine, bupivacaine, tetracaine, and combinations thereof.
29. A formulation as in claim 1, wherein the pain is musculoskeletal pain or inflammation and the drug includes a local anesthetic in base form.
30. A formulation as in claim 1, wherein the pain is musculoskeletal pain or inflammation and the drug includes a non-steroidal anti-inflammatory drug and the non-volatile solvent system is capable of generating a flux for the non-steroidal anti-inflammatory drug of at least 1 µg/cm2/hour.
31. A formulation as in claim 1, wherein the pain is musculoskeletal pain or inflammation and the drug includes a non-steroidal anti-inflammatory drug and the solidified layer is capable of generating a flux for the non-steroidal anti-inflammatory drug of at least 1 µg/cm2/hour.
32. A formulation as in claim 1, wherein the pain is musculoskeletal pain or inflammation drug includes a local anesthetic and the non-volatile solvent system is capable of generating a flux for the local anesthetic of at least 5 µg/cm2/hour.
33. A formulation as in claim 1, wherein the pain is musculoskeletal pain or inflammation and the drug includes a local anesthetic and the solidified layer is capable of generating a flux for the local anesthetic of at least 5 µg/cm2/hour.
34. A formulation as in claim 1, wherein the pain is neuropathic pain and the drug includes at least one member selected from the group consisting of local anesthetics, steroids, alpha-2 agonists, tricyclic anti-depressants, antiviral drugs, 5-HT2A receptor antagonists, and combinations thereof.
35. A formulation as in claim 1, wherein the pain is neuropathic pain and the drug includes at least one local anesthetic selected from the group consisting of lidocaine, bupivacaine, ropivacaine, tetracaine, and combinations thereof.
36. A formulation as in claim 35, the at least one local anesthetic is in free base form.
37. A formulation as in claim 1, wherein the pain is neuropathic pain and the drug includes dexamethasone.
38. A formulation as in claim 1, wherein the pain is neuropathic pain and the drug includes clonidine.
39. A formulation as in claim 1, wherein the pain is neuropathic pain and the drug is a tricyclic anti-depressant selected from the group consisting of amitriptyline, anticonvulsants, N-methyl-D-aspartate antagonists, ketamine, and combinations thereof.
40. A formulation as in claim 1, wherein the pain is neuropathic pain and the drug includes an antiviral drug, and the antiviral drug includes at least one member selected from the group consisting of acyclovir penciolovir, famciclovir, and valacyclovir.
41. A formulation as in claim 1, wherein the pain, is neuropathic pain and the drug includes ketanserin.
42. A formulation as in claim 1, wherein the pain is neuropathic pain and the drug includes an alpha-2 agonist and the non-volatile solvent system is capable of generating a flux of the alpha-2 agonist of at least 1 mcg/cm2/h.
43. A formulation as in claim 1, wherein the pain is neuropathic pain and the drug includes capsaicin and the non-volatile solvent system is capable of generating a flux of the capsaicin of at least 5 mcg/cm2/h.
44. A formulation as in claim 1, wherein the pain is neuropathic pain and the drug includes amitriptyline and the non-volatile solvent system is capable of generating a flux of the amitriptyline of at least 1 mcg/cm2/h.
45. A formulation as in claim 1, wherein the pain is neuropathic pain and the drug includes ketamine and the non-volatile solvent system is capable of generating a flux of the ketamine of at least 1 mcg/cm2/h.
46. A formulation as in claim 1, wherein the solidified layer is sufficiently flexible and adhesive to the skin such that when applied to the skin at a human joint, the solidified layer will remain substantially intact on the skin upon bending of the joint.
7. A formulation as in claim 1, wherein the volatile solvent system comprises a volatile solvent whose boiling point is below 20°C.
48. A formulation as in claim 47, wherein the volatile solvent with the boiling point below 20°C is completely dissolved in the formulation.
49. A formulation as in claim 47, wherein the volatile solvent with the boiling point below 20°C is included in the formulation as a propellant for pressurized spray-on application.
50 A formulation as in claim 47, wherein the volatile solvent with the boiling point below 20°C is a hydrofluorocarbon.
51. The formulation as in claim 47, wherein the at least one solvent whose boiling point is below 20°C includes at least one member selected from the group consisting of dimethyl ether, butane, 1,1, difluoroethane, 1,1,1,2 tetrafluorethane, 1,1,1,2,3,3,3-heptafluoropropane, 1,1,1,3,3,3 hexafluoropropane, and combinations thereof.
52. A formulation as in claim 1, wherein the formulation is formulated to deliver the drug at a therapeutically effective rate for at least about 2 hours following the formation of the solidified layer.
53. A formulation as in claim 1, wherein the formulation is formulated to deliver the drug at a therapeutically effective rate for at least about 4 hours following the formation of the solidified layer.
54. A formulation as in claim 1, wherein the formulation is formulated to deliver the drug at a therapeutically effective rate for at least about 8 hours following the formation of the solidified layer.
55. A formulation as in claim 1, wherein the formulation is formulated to deliver the drug at a therapeutically effective rate for at least about 12 hours following the formation of the solidified layer.
56. A formulation as in claim 1, wherein the solidifying agent is dispersed in the solvent vehicle.
57. A formulation as in claim 1, wherein the solidifying agent is solvated in the solvent vehicle.
58. A formulation as in claim 1, wherein the weight ratio of the non-volatile solvent system to the solidifying agent is from about 0.1:1 to about 10:1.
59. A formulation as in claim 1, wherein the weight ratio of the non-volatile solvent system to the solidifying agent is from about 0.5:1 to about 2:1.
60. A formulation as in claim 1, wherein the non-volatile solvent system is capable of causing human skin irritation and at least one non-volatile solvent of the non-volatile solvent system is capable of reducing the skin irritation.
61. A formulation as in claim 60, wherein the non-volatile solvent capable of reducing skin irritation includes at least one member selected from the group consisting of glycerin, propylene glycol, honey, and combinations thereof.
62. A formulation as in claim 1, wherein the solidified layer is formed within about 15 minutes of application to the skin surface under standard skin and ambient conditions.
63. A formulation as in claim 1, wherein the solidified layer is formed within 4 minutes of the application to the skin surface under standard skin and ambient conditions.
64. A formulation as in claim 1, wherein the formulation has an initial viscosity prior to skin application from about 100 cP to about 3,000,000 cP.
65. A formulation as in claim 1, wherein the formulation has an initial viscosity prior to skin application from about 1,000 cP to about 1,000,000 cP.
66. A formulation as in claim 1, wherein the weight percentage of the volatile solvent system is from about 10 wt% to about 85 wt%.
67. A formulation as in claim 1, wherein the weight percentage of the volatile solvent system is from about 20 wt% to about 50 wt%.
68. A formulation as in claim 1, wherein the non-volatile solvent system includes multiple non-volatile solvents, and at least one of the non-volatile solvents improves the compatibility of the non-volatile solvent system with the solidifying agent.
69. A formulation as in claim 1, wherein the non-volatile solvent includes at least two non-volatile solvents, and wherein one of the at least two non-volatile solvents is included to improve compatibility with the solidifying agent.
70. A formulation as in claim 1, wherein the solidified layer is coherent, flexible, and continuous.
71. A formulation as in claim 1, wherein the solidified layer, upon formation, is a soft, coherent solid that can be peeled from a skin surface as a single piece or as only a few large pieces relative to the application size.
72. A formulation as in claim 1, wherein the solidified layer is formulated to deliver the drug transdermally.
73. A method of dermally delivering a drug for treating musculoskeletal or neuropathic pain, comprising:
a) applying an adhesive solidifying formulation as in one of claims 1-71 to a skin surface of an subject experiencing pain, b) solidifying the formulation to form a solidified layer on the skin surface by at least partial evaporation of the volatile solvent system; and c) dermally delivering the drug from the solidified layer across the skin surface at therapeutically effective rates for treating the pain or inflammation of joints or muscles over a sustained period of time.
74. A method as in claim 73, wherein the formulation is applied onto a skin area over a wrist, ankle, elbow, or knee.
75. A method as in claim 73, wherein the formulation is applied onto a skin area over a finger or toe joint.
76. A method as in claim 73, wherein the formulation is applied onto a skin area over a back.
77. A method as in claim 73, wherein the formulation is applied onto a skin area over a neck.
78. A method as in claim 73, wherein the step of applying includes applying the formulation at a thickness from about 0.01 mm to about 3 mm.
79. A method as in claim 73, wherein the step of applying includes applying the formulation at a thickness from about 0.05 mm to about 1 mm.
80. A method as in claim 73, wherein the formulation is sprayed on the skin.
81. A method as in claim 73, wherein the formulation is applied on the skin using a manual pump.
82. A method as in claim 73, wherein the pain is neuropathic pain and is associated with shingles or postherpatic neuralgia.
83. A method as in claim 73, wherein the pain is neuropathic pain and is associated with postsurgical or post-traumatic pain.
84. A method as in claim 73, wherein the pain is neuropathic pain and is associated with diabetes.
85. A method as in claim 73, wherein the pain is musculoskeletal pain.
86. A solidified layer for treating pain, comprising:
a) a drug for treating musculoskeletal or neuropathic pain, b) a non-volatile solvent system including at least one non-volatile solvent, and c) a solidifying agent, wherein the solidified layer is capable of adhering to a skin surface and delivering the drug across the skin surface at therapeutically effective rates over a sustained period of time.
87. A solidified layer as in claim 86, wherein the solidified layer is formulated to be applied to a skin surface over a wrist, ankle, elbow, or knee.
88. A solidified layer as in claim 86, wherein the solidified layer is formulated to be applied to the skin surface over a finger or toe joint.
89. A solidified layer as in claim 86, wherein the solidified layer is formulated to be applied to the skin surface over a back, neck, shoulder, or hip.
90. A solidified layer as in claim 86, wherein the solidified layer has a thickness from about 0.01 mm to about 3 mm.
91. A solidified layer as in claim 86, wherein the pain is musculoskeletal pain and the drug includes at least one member from a class of drugs selected from the group consisting of non-steroidal anti-inflammatory drugs (NSAIDs), COX inhibitors, local anesthetics, 5HT-2A receptor antagonists, and -steroids, prodrugs thereof, and combinations thereof.
92. A solidified layer as in claim 86, wherein the pain is musculoskeletal pain drug includes at least one member selected from the group consisting of ketoprofen, diclofenac, lidocaine, ropivacaine, bupivacaine, tetracaine, ketanserin, and combinations thereof.
93. A solidified layer as in claim 86, wherein the pain is neuropathic pain and the drug includes at least one member selected from the group consisting of local anesthetics, steroids, alpha-2 agonists, tricyclic anti-depressants, antiviral drugs, 5-HT2A receptor antagonists, and combinations thereof.
94. A solidified layer as in claim 86, wherein the solidified layer is sufficiently flexible and adhesive to the skin such that when applied to the skin at a human joint, the solidified layer will remain substantially intact on the skin upon bending of the joint.
95. A solidified layer as in claim 86, wherein the solidified layer is formulated to deliver the drug at a therapeutically effective rate for at least about 2 hours.
96. A solidified layer as in claim 86, wherein the formulation is formulated to deliver the drug at a therapeutically effective rate for at least about 12 hours.
97. A solidified layer as in claim 86, wherein the weight ratio of the non-volatile solvent system to the solidifying agent is from about 0.5:1 to about 2:1.
98. A solidified layer as in claim 86, wherein the solidified layer is a soft, coherent solid layer that is peelable from a skin surface as a single piece or as only a few large pieces relative to the application size.
99. A solidified layer as in claim 86, wherein the solidified layer is a soft, coherent solid layer that is removable by washing.
100. A solidified layer as in claim 86, wherein the solidified layer is substantially devoid of water and solvents more volatile than water when the solidified layer contains no more than 10 wt% of water and solvents more volatile than water.
101. A solidified layer as in claim 86, wherein the solidified layer is substantially devoid of water and solvents more volatile than water when the solidified layer contains no more than 5 wt% of water and solvents more volatile than water.
102. A solidified layer as in claim 86, wherein the solidified layer is adhesive to the skin surface on one surface, and is non-adhesive on an opposing surface.
103. A solidified layer as in claim 86, wherein the solidified layer is flux-enabling for the drug.
CA2633515A 2005-12-14 2006-12-14 Compositions and methods for dermally treating pain Expired - Fee Related CA2633515C (en)

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Application Number Priority Date Filing Date Title
CA2747845A CA2747845C (en) 2005-12-14 2006-12-14 Compositions and methods for dermally treating pain

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
US75068305P 2005-12-14 2005-12-14
US75051905P 2005-12-14 2005-12-14
US75063705P 2005-12-14 2005-12-14
US60/750,683 2005-12-14
US60/750,637 2005-12-14
US60/750,519 2005-12-14
PCT/US2006/047926 WO2007070679A2 (en) 2005-12-14 2006-12-14 Compositions and methods for dermally treating pain

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CA2747845A Division CA2747845C (en) 2005-12-14 2006-12-14 Compositions and methods for dermally treating pain

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WO2007070679A3 (en) 2009-01-08
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EP1959931A2 (en) 2008-08-27
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