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WO2011041609A2 - Formulations topiques - Google Patents

Formulations topiques Download PDF

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Publication number
WO2011041609A2
WO2011041609A2 PCT/US2010/051001 US2010051001W WO2011041609A2 WO 2011041609 A2 WO2011041609 A2 WO 2011041609A2 US 2010051001 W US2010051001 W US 2010051001W WO 2011041609 A2 WO2011041609 A2 WO 2011041609A2
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WO
WIPO (PCT)
Prior art keywords
composition
etoricoxib
pharmaceutical composition
formulation
urea
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US2010/051001
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English (en)
Other versions
WO2011041609A3 (fr
Inventor
Servet Buyuktimkin
Nadir Buyuktimkin
Jagat Singh
John M. Newsam
Dominic King-Smith
Edward T. Kisak
Bradley S. Galer
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Nuvo Research Inc
Original Assignee
Nuvo Research Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Nuvo Research Inc filed Critical Nuvo Research Inc
Priority to EP10762838A priority Critical patent/EP2482850A2/fr
Publication of WO2011041609A2 publication Critical patent/WO2011041609A2/fr
Publication of WO2011041609A3 publication Critical patent/WO2011041609A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
    • 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
    • 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
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/38—Cellulose; Derivatives thereof
    • 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
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Definitions

  • Osteoarthritis is a chronic joint disease characterized by progressive degeneration of articular cartilage. Symptoms include joint pain and impaired movement. OA is one of the leading causes of disability worldwide and a major financial burden to health care systems. It is estimated to affect over 15 million adults in the United States alone. See Boh, L.E.; Osteoarthritis. In: DiPiro, J.T.; Talbert, R.L.; Yee, G.C. et al. editors.
  • COX cyclooxygenase
  • the COX enzyme has two isoforms, COX-1 and COX-2.
  • Traditional NSAIDs inhibit both isoforms of the COX enzyme, while the selective COX-2 (coxib) class of NSAIDs preferentially inhibits COX-2.
  • NSAIDs have analgesic, anti-inflammatory, and antipyretic effects and are useful in reducing pain and inflammation. They are, however, associated with serious potential side effects including nausea, vomiting, peptic ulcer disease, and gastrointestinal (GI) hemorrhage. Although selective COX-2 inhibitors produce fewer GI side effects, they may increase the risk of thrombotic events (e.g., stroke or heart attack). Because of this potential side effect, most of the selective COX-2 inhibitors have been withdrawn from the U.S.
  • Pennsaid GelTM is a topical formulation comprising diclofenac sodium that overcomes disadvantages of prior art NSAID formulations.
  • U.S. Patent Publication No. 2008/0300311 PennsaidTM solution has been shown in clinical trials to be effective for treating the pain and symptoms of osteoarthritis, and it has been approved for use in Canada, the U.S., and several European countries.
  • a topical drug containing a COX-2 selective inhibitor would offer patients an attractive new treatment modality. Such a drug could minimize systemic exposure to the active pharmaceutical ingredient by localizing the drug at the site of action.
  • a topical coxib might have even better GI safety profile than topical formulations containing traditional NSAIDs, making it particularly suitable for patients at risk of GI bleeds.
  • the skin barrier can be compromised by several physical methods, such as iontophoresis, ultrasound, electroporation, heat, and microneedles.
  • Molecular penetration enhancers are a preferred means for reversibly lowering the skin barrier. At least 400 chemicals have been identified as skin permeability enhancers.
  • General categories of MPETMs include pyrrolidones, fatty acids, fatty acid esters, fatty acid alcohols, sulfoxides, essential oils, terpenes, oxazolidines, surfactants, polyols, azone and derivatives, and epidermal enzymes.
  • MPETMs The challenge with use of MPETMs is that few seem to induce a significant or therapeutic enhancement of drug transport at tolerable levels. This is because a MPE 's disruption of the skin barrier can potentially cause skin irritation. With increased disruption, skin irritation is expected to become a greater issue. This is particularly problematic with topical OA treatments where the goal is to have the active penetrate deeply into joint tissue and where the drug must be used on a long-term basis due to the nature of the disease.
  • the present invention provides pharmaceutical compositions, methods for preparation, and methods of treatment comprising a selective COX-2 inhibitor, a lower amino alcohol, a cellulosic thickening agent, and urea.
  • the selective COX-2 inhibitor is etoricoxib.
  • the formulations enhance permeability and bioavailability, and they are useful for topical treatment of pain and/or inflammation.
  • the method of treatment is directed to pain associated with OA.
  • the present invention provides a pharmaceutical composition for topical administration, the composition consisting of, consisting essentially of, or comprising a selective COX-2 inhibitor (e.g. , etoricoxib), a lower amino alcohol, a cellulosic thickening agent, urea, a lower alcohol, and water.
  • a selective COX-2 inhibitor e.g. , etoricoxib
  • the composition comprises 0.1% to 5% (w/w) etoricoxib, 0.5% to 5% of a lower amino alcohol, 0.5% to 5% of a cellulosic thickening agent, 0.5% to 10% urea, 35% to 65% of a lower alcohol, and 15% to 30% of water.
  • the composition comprises 1% to 3% (w/w) of a selective COX-2 inhibitor. Still more preferably, the composition comprises 1% (w/w) of a selective COX-2 inhibitor. Alternatively, the composition comprises 2% (w/w) of a selective COX-2 inhibitor. Alternatively or yet still more preferably, the selective COX-2 inhibitor is etoricoxib.
  • the lower amino alcohol is 2-amino-2-methylpropanol ("AMP")-
  • AMP 2-amino-2-methylpropanol
  • the lower alcohol is a monohydric alcohol.
  • the composition further comprises an additional molecular penetration enhancer (MPE ). More preferably, the MPETM is the lower alcohol 2-(2-ethoxyethoxy)ethanol (Transcutol ® ). Still more preferably, the composition comprises 5% to 25% (w/w) 2-(2-ethoxyethoxy)ethanol, and yet still more preferably, 10% 2-(2-ethoxyethoxy)ethanol.
  • MPETM is the lower alcohol 2-(2-ethoxyethoxy)ethanol
  • Transcutol ® the lower alcohol 2-(2-ethoxyethoxy)ethanol
  • the composition comprises 5% to 25% (w/w) 2-(2-ethoxyethoxy)ethanol, and yet still more preferably, 10% 2-(2-ethoxyethoxy)ethanol.
  • the MPETM is a terpene. More preferably, the terpene is selected from the group consisting of limonene, geraniol and mixtures thereof. Still more preferably, the composition comprises 0.1% to 5% (w/w) terpene, and yet still more preferably, 3% terpene. [0023] In yet still another aspect of the embodiment or preferred aspect, the composition further comprises a nonionic surfactant. More preferably, the nonionic surfactant is a polysorbitan ester. Still more preferably, the polysorbitan ester is polysorbate 20 (Tween ® 20).
  • the composition comprises from 0.5% to 15% (w/w) nonionic surfactant, and yet still more preferably, 2% to 10% nonionic surfactant.
  • the present invention provides a pharmaceutical composition for topical administration, the composition consisting of, consisting essentially of, or comprising 1 to 3% (w/w) etoricoxib, 0.5% to 3% AMP, 1% to 3% hydroxypropyl cellulose, 2% to 10% urea, 10% 2-(2-ethoxyethoxy)ethanol, a lower monohydric alcohol, and water.
  • said composition consists of, consists essentially of, or comprises 2% to 5% urea.
  • said composition consists of, consists essentially of, or comprises about 7.5% urea.
  • the present invention provides a method for topically treating pain in a subject, the method comprising topically applying a pharmaceutical composition to treat pain in the subject; the composition consisting of, consisting essentially of, or comprising a selective COX-2 inhibitor (e.g., etoricoxib), a lower amino alcohol, a cellulosic thickening agent, urea, a lower alcohol, and water.
  • a selective COX-2 inhibitor e.g., etoricoxib
  • the composition comprises 0.1% to 5% (w/w) etoricoxib, 0.5% to 5% of a lower amino alcohol, 0.5% to 5% of a cellulosic thickening agent, 0.5% to 10% urea, a lower alcohol, and water.
  • FIG. 2 describes etoricoxib permeation through porcine skin from a second series of topical formulations (Table 2) at 4, 21, and 26 hours after application.
  • FIG. 3 describes etoricoxib permeation through porcine skin from a third series of topical formulations (Table 3) at 4 and 20 hours after application at two different dosing levels.
  • FIG. 4 describes etoricoxib permeation through porcine skin from a fourth series of topical formulations (Table 4) at 4, 20, and 24 hours after application.
  • FIG. 6 describes etoricoxib permeation through porcine skin from a sixth series of topical formulations (Table 6) at 4, 21, and 26 hours after application.
  • FIG. 7 describes etoricoxib permeation through porcine skin from a further series of topical formulations (Table 8) at 4, 21, and 26 hours after application.
  • FIG. 8 describes etoricoxib permeation through porcine skin from a further series of topical formulations (Table 9) at 4, 21, and 26 hours after application.
  • FIG. 9 describes etoricoxib permeation through porcine skin from a further series of topical formulations (Table 10) at 4, 21, and 26 hours after application. DETAILED DESCRIPTION OF THE INVENTION I. Definitions
  • a not only include aspects with one member, but also include aspects with more than one member.
  • an embodiment including "a cellulosic thickening agent and a lower monohydric alcohol” should be understood to present certain aspects with at least a second cellulosic thickening agent, at least a second lower monohydric alcohol, or both.
  • the term "about” as used herein includes a close (i.e., narrow) range around the explicit value for a variable. For example, in certain instances the term “about” includes 5%- 10% higher or 5-10% lower than the value given. For example, “about 10” includes the range of values from 9.5 to 10.5.
  • Cellulosic thickening agent includes a thickening agent that is a natural or synthetic polymeric carbohydrate (e.g., cellulose, pharmaceutically acceptable vegetable gums) or a polymeric or oligomeric derivative of a polymeric carbohydrate that is produced by chemical modification (e.g. , hydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose).
  • Representative cellulosic thickening agents include cellulose, hydroxypropyl cellulose ("HPC"), hydroxypropyl methyl cellulose, hydroxyethyl cellulose, methyl cellulose, carboxymethyl cellulose, and the like.
  • Finite dosing generally includes an application of a limited reservoir of an active agent.
  • the active agent in the reservoir is depleted with time, leading to a tapering off of the absorption rate of the active agent after a maximum absorption rate is reached.
  • composition as used herein are equivalent terms referring to a composition of matter suitable for pharmaceutical use.
  • “Infinite dosing” as used herein generally includes an application of a large reservoir of an active agent. The active agent in the reservoir is not significantly depleted with time, thereby providing protracted, continuous, steady-state absorption of the active.
  • “Lower amino alcohol” as used herein includes straight- or branched-chain alkyl compounds of 2 to 8 carbon atoms, and preferably, of 2 to 6 carbon atoms.
  • Representative lower amino alcohols include 2-amino-2-methylpropanol, meglumine, serine methyl ester, serine ethyl ester, threonine ethyl ester, and the like.
  • “Lower alcohol” as used herein includes straight- or branched-chain alkyl alcohols of 1 to 6 carbon atoms.
  • Representative lower monohydric alcohols include methanol, ethanol, n-propanol, isopropanol, n-butanol, t-butanol, n-pentanol, 3-pentanol, 2- methoxyethanol, propylene glycol, and the like.
  • “Monohydric alcohol” as used herein includes straight- or branched-chain alkyl alcohols with a single hydroxyl group.
  • Representative monohydric alcohols include methanol, ethanol, n-propanol, isopropanol, n-butanol, t-butanol, n-pentanol, 3-pentanol, 2- methoxyethanol, 2-(2-ethoxyethoxy)ethanol, oleyl alcohol, and the like.
  • “Nonionic surfactant” as used herein indicates a surface-active agent that is uncharged under the conditions of the formulation.
  • Representative nonionic surfactants include the polysorbitans (e.g., polysorbitan 20), fatty acid esters (e.g., isopropyl myristate), and the like.
  • compositions comprising A or B would typically present an aspect with a composition comprising both A and B.
  • Or should, however, be construed to exclude those aspects presented that cannot be combined without contradiction (e.g., a formulation pH that is between 9 and 10 or between 7 and 8).
  • Penetration enhancer includes an agent or a combination of agents that improves the transport of molecules such as a pharmaceutically or cosmetically active agent into or through a natural membrane such as skin or nail.
  • a pharmaceutically or cosmetically active agent into or through a natural membrane such as skin or nail.
  • Various conditions may occur at different sites in the body, either in the skin or below the skin, creating a need to target delivery of compounds. For example, in a treatment for osteoarthritis, delivery of the active agent to the underlying tissues surrounding the joint may be necessary to achieve therapeutic benefit.
  • An MPETM may be used to assist in the delivery of an active agent i) directly into the skin or nail; ii) locally, or regionally, into tissue underlying or near to the skin or nail; or iii) indirectly via systemic distribution to the site of the disease. If systemic distribution of an active agent would be likely to produce side effects (e.g., etoricoxib), an MPETM is preferably selected to maximize direct delivery and to minimize systemic distribution.
  • An MPETM may be a pure substance or may comprise, consist essentially of, or consist of a mixture of different chemical entities. [0053] "Thickening agent" as used herein includes an agent or combination of agents that increases the viscosity of a formulation.
  • a thickening agent may be a pure substance, or it may comprise, consist essentially of, or consist of a mixture of different chemical entities.
  • Exemplary thickening agents include cellulosic thickening agents, carbomer polymers, carbomer derivatives, cellulose derivatives, polyvinyl alcohol, poloxamers, polysaccharides, and mixtures thereof.
  • Topical formulation includes a formulation that is suitable for topical application to the skin, a nail, or a mucosa.
  • a topical formulation may, for example, be used to confer a therapeutic or cosmetic benefit to its user.
  • Topical formulations can be used for topical, local, regional, or transdermal application of substances.
  • Transdermal as used herein includes a process that occurs through the skin. The terms “transdermal,” “percutaneous,” and “transcutaneous” can be used interchangeably. In certain embodiments, “transdermal” may also include epicutaneous.
  • Transdermal application as used herein includes administration through the skin. Transdermal application can be used for systemic delivery of an active agent; however, it is also useful for delivery of an active agent to tissues underlying the skin with minimal systemic absorption. In certain embodiments, "transdermal application” may also include epicutaneous application.
  • the present invention provides a pharmaceutical composition comprising, consisting essentially of, or consisting of a selective COX-2 inhibitor.
  • the selective COX-2 inhibitor is selected from the group of celecoxib, etoricoxib, lumiracoxib, parecoxib, rofecoxib, valdecoxib and a combination thereof. More preferably, the selective COX-2 inhibitor is selected from the group of celecoxib, etoricoxib, and rofecoxib. Still more preferably, the selective COX-2 inhibitor is etoricoxib.
  • the pharmaceutical composition comprises 0.1% to 5% (w/w) of etoricoxib, preferably 1% to 3%, and more preferably 2%.
  • a composition permits delivery of a selective COX-2 inhibitor daily dosage of about 0.01 mg to about 120 mg, preferably about 0.1 mg to 60 mg, more preferably about 1 mg to about 30 mg, and still more preferably about 1 to about 10 mg. Yet still more preferably, the formulation permits delivery of a daily dosage of about 3 mg.
  • the concentration is such that this dosage amount can be provided by application of the composition from one to four times a day, preferably one to two times a day, to a skin area of up to about 2500 cm 2 , preferably about 1200 to 1800 cm 2 (750 cm 2 /knee).
  • the composition can be applied to a skin area of about 1 to 50 cm , about 50 to 250 cm , about 100 to 500 cm 2 , about 200 to 800 cm 2 , or about 800 to 1200 cm 2 .
  • the dosage and application area will vary and can be tailored to the area being treated (e.g. , knees, fingers, toes, back, and the like).
  • a single knee is treated and the application area is about 750 cm 2 .
  • both knees of an individual are treated and the application area is about 1500 cm 2 (about 750 cm 2 per knee).
  • the formulation of the present invention provides a total or a systemic dose that is less than 50% of the systemic daily dose of the maximum approved oral dose; preferably less than 25%, more preferably less than 10%, and most preferably less than 5%, yet provides local or regional delivery levels sufficient for therapeutic benefit.
  • the concentration is such that this dosage amount can be provided by application of the composition from one to four times a day, preferably one to two times a day, to a skin area of up to about 2500 cm 2 , preferably about 1200 to 1800 cm 2 (750 cm 2 /knee).
  • the composition can be applied to a skin area of about 1 to 50 cm , about 50 to 250 cm 2 , about 100 to 500 cm 2 , about 200 to 800 cm 2 , or about 800 to 1200 cm 2 .
  • this comparative formulation comprises etoricoxib. More preferably, the flux of etoricoxib is at least 1.5 times greater than the flux of the comparative formulation's active. In other words, the ratio of: (i) the composition's etoricoxib flux to (ii) the comparative formulation's coxib flux is preferably greater than 1.0, and more preferably at least about 1.5.
  • the composition has an etoricoxib flux that is at least 2.0 times greater than the comparative formulation's coxib flux. Yet still more preferably, the composition has an etoricoxib flux that is at least 4.0 times greater than the comparative formulation's coxib flux.
  • the composition has a selective COX-2 inhibitor flux equal to or greater than the selective COX-2 inhibitor flux from a known comparative formulation with the same selective COX-2 inhibitor.
  • the selective COX-2 inhibitor flux is greater than the flux of the comparative formulation with the same selective COX-2 inhibitor. More preferably, the selective COX-2 inhibitor flux is at least 1.5 times greater than the flux of a comparative formulation with the same selective COX-2 inhibitor.
  • the ratio of: (i) the selective COX-2 inhibitor flux of the composition to (ii) the selective COX-2 inhibitor flux from a comparative formulation with the same selective COX-2 inhibitor is preferably greater than 1.0, and more preferably at least about 1.5.
  • compositions contain AMP, cellulosic thickener, urea, and a terpene (i.e., limonene, geraniol) at different levels.
  • the amount of formulation applied to each donor cell was 25 ⁇ , except for IIIA and IIIB (50 ⁇ ).
  • Various alcohol mixtures were used as solvents.
  • Polysorbitans (especially polysorbate 20) were added at different levels as non-ionic surfactants.
  • the etoricoxib concentration was maintained at 2% for all formulations; a formulation containing 2% etoricoxib, 48% ethanol and 50% water was included as a control.
  • the etoricoxib-delivery enhancement ratios were calculated as the ratios of etoricoxib delivery from test formulations to those from the control formulation.
  • Transcutol ® may be important for stability.
  • AMP The incorporation of AMP enhanced the etoricoxib delivery (F80 vs. F86).
  • DL-Limonene The optimal DL-limonene concentration in enhancing etoricoxib delivery across intact pig skin appears to be 3%. Reducing the DL-limonene levels to 0 or 1.5% led to reduced etoricoxib delivery (F80 vs. F87 and F88).
  • Transcutol ® Transcutol ® at 10% concentration is optimal. Removing Transcutol ® from the formulation or reducing the Transcutol ® concentration to a lower level (i.e., 5%) led to reduction of the etoricoxib delivery (F80 vs. F90 and F89).
  • HY121 a second HPC gelling agent
  • HY121 a second HPC gelling agent
  • both water and HY121 concentrations were maintained as constants while varying the concentrations of other excipients.
  • Visual inspection of formulations incorporating either HY117 or HY121 as the gelling agent indicated that HY121 is a more effective gelling agent for this particular formulation and produces the desired formulation viscosity of the final formulation.
  • AMP Increasing the AMP concentration beyond the 1.5% level led to formulation instability (F95 and F96) in this study.
  • Transcutol ® Removing Transcutol ® from the formulation or reducing to a 5% level led to reduction of the etoricoxib permeation (F100 and F101).

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Rheumatology (AREA)
  • Pain & Pain Management (AREA)
  • Organic Chemistry (AREA)
  • Inorganic Chemistry (AREA)
  • Dermatology (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne des compositions pharmaceutiques topiques, des méthodes de préparation, et des méthodes de traitement mettant en œuvre un inhibiteur sélectif de COX-2 utile pour le traitement de la douleur, en particulier la douleur associée à l'arthrose. Les compositions de l'invention offrent une bonne perméabilité et biodisponibilité sur le site cible. Dans certains modes de réalisation préférés, on décrit une composition comprenant étoricoxib, 2-amino-2-méthylpropanol (AMP), un épaississant cellulosique, et de l'urée.
PCT/US2010/051001 2009-09-30 2010-09-30 Formulations topiques Ceased WO2011041609A2 (fr)

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US24722209P 2009-09-30 2009-09-30
US61/247,222 2009-09-30

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011149645A1 (fr) * 2010-05-28 2011-12-01 Nuvo Research Inc. Formulation topique d'étoricoxib
US9144553B2 (en) 2012-12-21 2015-09-29 Teikoku Pharma Usa, Inc. Compositions and methods for transdermal delivery of hormones and other medicinal agents
US11357792B2 (en) 2017-09-15 2022-06-14 Dyvve Biosciences, Inc. Method of administration and treatment
US11491225B2 (en) 2014-12-23 2022-11-08 Dyve Biosciences, Inc. Transdermal carrier

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20080300311A1 (en) 2006-10-17 2008-12-04 Nuvo Research Diclofenac gel

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
HUP0600294A2 (en) * 2001-05-31 2007-02-28 Pharmacia Corp Skin-permeable selective cyclooxygenase-2 inhibitor composition
US20050020658A1 (en) * 2002-11-21 2005-01-27 Katsuyuki Inoo Selective cyclooxygenase-2 inhibitor patch
WO2005044227A1 (fr) * 2003-11-05 2005-05-19 Glenmark Pharmaceuticals Limited Compositions pharmaceutiques topiques

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20080300311A1 (en) 2006-10-17 2008-12-04 Nuvo Research Diclofenac gel

Non-Patent Citations (10)

* Cited by examiner, † Cited by third party
Title
BELLAMY, N.; KIRWAN, J.; BOERS, M.; BROOKS, P.; STRAND, V.; TUGWELL, P. ET AL.: "Recommendations for a core set of outcome measures for future Phase III clinical trials in knee, hip and hand osteoarthritis. Consensus development at OMERACT IIL", J RHEUMATOL, vol. 24, 1997, pages 799 - 802
BOH, L.E. ET AL.: "Pharmacotherapy: a pathophysiological approach", 1999, APPLETON & LANGE, article "Osteoarthritis", pages: 1441 - 59
HO ET AL.: "The influence of cosolvents on the in-vitro percutaneous penetration of diclofenac sodium from a gel system", J. PHARM. PHARMACOL., vol. 46, 1994, pages 636 - 642
LIN ET AL.: "Efficacy of topical non-steroidal anti-inflammatory drugs in the treatment of osteoarthritis: meta- analysis of randomized controlled trials", BMJ, 2004
NAITO ET AL.: "Percutaneous absorption of diclofenac sodium ointment", INT. JOUR. OF PHARMACEUTICS, vol. 24, 1985, pages 115 - 124
OBATA, INTERNATIONAL JOURNAL OF PHARMACEUTICS, vol. 89, 1993, pages 191 - 198
OSBORNE, D.W.; HENKE, J. J.: "Skin Penetration Enhancers Cited in the Technical Literature", PHARMACEUT. TECH., November 1997 (1997-11-01), pages 58 - 66
OSTRENGA, J. ET AL.: "Significance of vehicle composition I: relationship between topical vehicle composition, skin penetrability, and clinical efficacy", JOURNAL OF PHARMACEUTICAL SCIENCES, vol. 60, 1971, pages 1175 - 1179
RHEUM. DIS. CLIN NORTH AM., vol. 25, 1999, pages 899 - 918
WILLIAMS; BARRY: "Penetration Enhancers", ADVANCED DRUG DELIVERY REVIEWS, vol. 56, 2004, pages 603 - 618

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