WO2016137411A1 - Composition de spray topique comprenant de l'ibuprofène et de la lidocaïne - Google Patents

Composition de spray topique comprenant de l'ibuprofène et de la lidocaïne Download PDF

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Publication number
WO2016137411A1
WO2016137411A1 PCT/TR2015/000069 TR2015000069W WO2016137411A1 WO 2016137411 A1 WO2016137411 A1 WO 2016137411A1 TR 2015000069 W TR2015000069 W TR 2015000069W WO 2016137411 A1 WO2016137411 A1 WO 2016137411A1
Authority
WO
WIPO (PCT)
Prior art keywords
ibuprofen
pharmaceutical composition
lidocaine
composition according
topical
Prior art date
Application number
PCT/TR2015/000069
Other languages
English (en)
Inventor
Ersin Yildirim
Başak Acar KARAKÖY
Kerim AKKAYA
Tolga Ramazan KARASU
Fatih Cengiz Aygül
Kübra GENCER
Original Assignee
Pharmactive İlaç Sanayi Ve Ticaret A. Ş.
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 Pharmactive İlaç Sanayi Ve Ticaret A. Ş. filed Critical Pharmactive İlaç Sanayi Ve Ticaret A. Ş.
Priority to PCT/TR2015/000069 priority Critical patent/WO2016137411A1/fr
Publication of WO2016137411A1 publication Critical patent/WO2016137411A1/fr

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Classifications

    • 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
    • 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
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
    • 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
    • A61K9/10—Dispersions; Emulsions
    • A61K9/12—Aerosols; Foams
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P23/00—Anaesthetics
    • A61P23/02—Local anaesthetics

Definitions

  • This invention relates to a stable pharmaceutical compositions providing active ingredients such as ibuprofen and lidocaine. This invention also relates to the symptomatic relief of severe sore throats, topical treatment of backache, muscular pain, sprains, and neuralgia.
  • Ibuprofen chemical name is 2-(4-isobutylphenyl) propionic acid, is a well-known antiinflammatory drug having a molecular weight of 206.28. Ibuprofen is now marketed generically and is patented in the 60's.
  • Ibuprofen is a racemic mixture, it is only the racemic mixture which has in fact ever been marketed.
  • the S(+) enantiomer is the active form of ibuprofen.
  • the present invention relates to topical compositions of ibuprofen and methods for making and using the compositions.
  • Past formulations of ibuprofen have chiefly made use of the water- based form (salt form) of ibuprofen.
  • Ibuprofen in its salt forms the basis of such drug products as Advil(R) (potassium salt form of ibuprofen).
  • Use of ibuprofen in its free acid form has been limited to formulations intended for oral administration, e.g., Motrin(R) in tablet and oral suspension.
  • Lidocaine chemical name is 2-(diethylamino)- W-(2,6-dimethylphenyl)acetamide, is a well known local anesthetic drug belongs to class-1b antiarrhytmic drugs having a molecular weight of 234.34.
  • Lidocaine the first amino amide type local anesthetic, was first synthesized under the name 'xylocaine'.
  • Lidocaine is commonly used topically to relieve itching, burning, and pain from skin inflammations, injected as a dental anesthetic, or as a local anesthetic for minor surgery.
  • Lidocaine is used for the purpose of local or topical anesthesia.
  • the general usage form of lidocaine is an external preparation comprising lidocaine or a patch comprising lidocaine.
  • Examples of external preparations include ointment, cream, gel, spray, etc., which are used, for example, for topical anesthesia of the skin in the treatment of postherpetic neuralgia.
  • Lidocaine viscous solution is a local anesthetic that is applied topically to treat painful mucous membranes or throat pain associated with oral diseases and for procedures involving the mouth or throat. Lidocaine provides pain relief by inhibiting the influx of sodium ions involved in the initiation and conduction of nerve impulses associated with the perception of pain.
  • EP2373346 A1 discloses a pharmaceutical topical composition comprising ibuprofen.
  • EP1126830 relates to a pharmaceutically acceptable composition for external use which comprises a non-steroidal anti-inflammatory agent, an anesthetic agent and the skin penetration enhancer.
  • Ibuspray marketed by Dermal Laboratories.
  • Dequaspray marketed by Reckitt Benckiser Healthcare and Vemcaine marketed by Vem Pharmaceuticals comprises Iidocaine. But there is not any combined composition consisting of ibuprofen and Iidocaine used as sprays.
  • the present invention relates to topical administration comprising ibuprofen, Iidocaine and one or more pharmaceutically acceptable excipients, to a patient suffering muscular pain, strain, sore throats and mouth pains supported with anesthesia effect.
  • the invention provides a pharmaceutical composition in the form of topical spray consisting essentially of:
  • active ingredients and excipients are mixed to form a sprayable topical formulation.
  • the invention discloses novel pharmaceutical combinations and methods for the treatment or prevention of muscular pain, sprain with the help of anesthetics.
  • the present invention provides pain treatment with the help of anesthesia effect.
  • Muscular pain and sprain need to be anaesthetized in some conditions for example; after sport injuries, backache pains, wound healing after a surgery.
  • present invention relates to not only treating the pain but also anesthesizing the part of the body that feels pain.
  • present invention has an advantage in the treatment of pain compared to composition that contains only one active ingredient.
  • pharmaceutical composition may be formulated in the form suitable for topical administration such as ointment, gel, cream, lotion, spray, plaster, solution.
  • the components of the pharmaceutical composition according to the present invention are brought together into a spray for topical administration according to standard practice and procedures well known to one of ordinary skill in the art using conventional formulation and manufacturing techniques.
  • present invention is a pharmaceutical composition containing ibuprofen and lidocaine; both active ingredients being present in the free state or in the form of a salt, solvate or enantiomer.
  • the active ingredients are generally formulated in the spray form containing from 1 to 20 mg of ibuprofen and 1 to 20 mg of lidocaine per 100 ml_, preferably 5 mg of each active agents.
  • composition of the present invention comprises ibuprofen and lidocaine, in combination with at least one pharmaceutically acceptable excipient.
  • composition of this invention may comprise C1-C4 alcoholic solvents selected from methanol, ethanol, denatured alcohol, n-propanol, isopropanol and butanol.
  • prefered solvent is either isopropanol and/or denatured alcohol. Surprisingly these solvents make composition higher stable than other solvents do.
  • the process of preparing the stable pharmaceutical composition comprises steps of preparing a first part of composition comprising ibuprofen or salt, solvate, enantiomer thereof, and lidocaine or salt, solvate, enantiomer thereof and separately preparing second part comprising at least one C1-C4 alcohol, at least one polymer and optionally at least one preservative and/or fragrance followed by mixing two parts and making up volume with purified water.
  • Polymers can be selected from the group, but are not limited to, polypropylene glycol, polyethylene glycols (PEG) as macrogol or cetomacrogol, hydroxypropylmethyl cellulose, hydroxypropyl cellulose, ethyl cellulose. A mixture of polymers may also be used. A preferred polymer is polyethylene glycol.
  • the antiinflammatory and anesthetic pharmaceutical preparation of this invention may comprise water soluble polymers such as carboxymethyl cellulose, polivinyl alcohol, polypropylene glycol, polyethylene glycols, hydroxypropyl cellulose etc. Such a polymer may be applied at 0.1 to 15% by weight based upon a total weight at the preparation for external use.
  • Preservatives can be selected from the group, propyl gallate, propyl paraben, sodium nitrate, benzoic acid, sodium benzoate, hydroxybenzoate, propionic acid, sodium propionate, sulfur dioxide, sulfites, sorbic acid and sodium sorbate.
  • Propyl paraben is prefered.
  • Fragrances can be selected from groups, but are not limited to, esters, amines, terpenes, aromatics, such as menthol, acetaldehyde, fructone, acetoin, furaneol, isoveraldehyde, vanilin, annisol, cadaverine, terpineol and other materials known to one of ordinary skill in the art.
  • the present invention consists of ibuprofen and lidocaine resulting in a topical spray.
  • Examples for pharmaceutical compositions combining Ibuprofen and Lidocaine are shown below.
  • Ethanol and cetomacrogol are mixed to form the first part of the solution.
  • Separately ibuprofen and lidocaine hydrochloride are mixed in a different container to form the second part.
  • the first part is added into the second part.
  • the mixture is made up volume with purified water by addition of fragrances. The formulation seemed viscous.
  • Example 1 First part is formed with ethanol and macrogol and the second part with ibuprofen and lidocaine hydrochloride. And the mixture is made up volume with purified water. The used ethanol amount is increased and polyethylene glycol amount is decreased. By this way, the formulation was found to be satisfactory but slightly oily.
  • first part is formed with ethanol and macrogol and the second part with ibuprofen and lidocaine hydrochloride. Fragrances are added and the mixture is made up 100 mL volume with purified water. The formulation was found to be satisfactory. In this case, lidocaine hydrochloride is used instead of lidocaine base. But much more impurity was observed in this batch compared to example 4. The impurity results are shown at table .
  • first part is formed with ethanol and macrogol and the second part with ibuprofen and lidocaine base, and the mixture is made up 100 mL volume with purified water.
  • the formulation was found to be satisfactory, and less impurity was observed in this batch compared to example 4 and 5 because of using less amount of ethanol. The impurity results are shown at table 1.
  • Example 7
  • first part is formed with ethanol and macrogol and the second part with ibuprofen and lidocaine base, and the mixture is made up 100 mL volume with purified water.
  • the formulation was found to be good.
  • isopropanol instead of ethanol has changed the stability results in a good way. Less impurity was observed in this batch compared to other examples shown at table 1.
  • first part is formed with ethanol, propyl paraben and macrogol and the second part with ibuprofen and lidocaine base, and the mixture is made up 100 mL volume with purified water.
  • the best formulation is obtained by using isopropanol and propyl paraben instead of ethanol and by using lidocaine base instead of lidocaine HCI.
  • the comparative results are shown at Table 1.

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

Abstract

La présente invention concerne la préparation d'une composition pharmaceutique topique stable comprenant de l'ibuprofène et de la lidocaïne. De préférence, la composition est un spray topique.
PCT/TR2015/000069 2015-02-25 2015-02-25 Composition de spray topique comprenant de l'ibuprofène et de la lidocaïne WO2016137411A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/TR2015/000069 WO2016137411A1 (fr) 2015-02-25 2015-02-25 Composition de spray topique comprenant de l'ibuprofène et de la lidocaïne

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/TR2015/000069 WO2016137411A1 (fr) 2015-02-25 2015-02-25 Composition de spray topique comprenant de l'ibuprofène et de la lidocaïne

Publications (1)

Publication Number Publication Date
WO2016137411A1 true WO2016137411A1 (fr) 2016-09-01

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3342397A1 (fr) * 2016-12-31 2018-07-04 Abdi Ibrahim Ilac Sanayi ve Ticaret A.S. Spray pharmaceutique comprenant de la naproxen and lidocaine base
DE202022105222U1 (de) 2022-06-14 2023-09-22 Maria Clementine Martin Klosterfrau Vertriebsgesellschaft mit beschränkter Haftung Kombinationstherapeutikum
WO2023241838A1 (fr) 2022-06-14 2023-12-21 Maria Clementine Martin Klosterfrau Vertriebsgesellschaft Mbh Agent thérapeutique combiné

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0250802A1 (fr) * 1986-06-24 1988-01-07 Merckle GmbH Préparations d'ibuprofène liquides
US5885597A (en) * 1997-10-01 1999-03-23 Medical Research Industries,Inc. Topical composition for the relief of pain
EP1126830A1 (fr) 1998-11-06 2001-08-29 Bristol-Myers Squibb Company Preparations pharmaceutiques a usage externe contenant des agents anti-inflammatoires et analgesiques non-steroidiens
EP2373346A2 (fr) 2008-09-10 2011-10-12 BioChemics, Inc. Ibuprofène destiné à être administré de manière topique
MX2010012927A (es) * 2010-11-26 2012-05-28 Pharmacos Exakta Sa De C V Una mezcla solubilizante, solucion farmaceutica para tratar otitis y su metodo de preparacion.

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0250802A1 (fr) * 1986-06-24 1988-01-07 Merckle GmbH Préparations d'ibuprofène liquides
US5885597A (en) * 1997-10-01 1999-03-23 Medical Research Industries,Inc. Topical composition for the relief of pain
EP1126830A1 (fr) 1998-11-06 2001-08-29 Bristol-Myers Squibb Company Preparations pharmaceutiques a usage externe contenant des agents anti-inflammatoires et analgesiques non-steroidiens
EP2373346A2 (fr) 2008-09-10 2011-10-12 BioChemics, Inc. Ibuprofène destiné à être administré de manière topique
MX2010012927A (es) * 2010-11-26 2012-05-28 Pharmacos Exakta Sa De C V Una mezcla solubilizante, solucion farmaceutica para tratar otitis y su metodo de preparacion.

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3342397A1 (fr) * 2016-12-31 2018-07-04 Abdi Ibrahim Ilac Sanayi ve Ticaret A.S. Spray pharmaceutique comprenant de la naproxen and lidocaine base
DE202022105222U1 (de) 2022-06-14 2023-09-22 Maria Clementine Martin Klosterfrau Vertriebsgesellschaft mit beschränkter Haftung Kombinationstherapeutikum
DE102022123723A1 (de) 2022-06-14 2023-12-14 Maria Clementine Martin Klosterfrau Vertriebsgesellschaft mit beschränkter Haftung Kombinationstherapeutikum
WO2023241838A1 (fr) 2022-06-14 2023-12-21 Maria Clementine Martin Klosterfrau Vertriebsgesellschaft Mbh Agent thérapeutique combiné

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