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WO2011027365A9 - Compositions ophtalmiques contenant du dorzolamide, du timolol et de la brimonidine - Google Patents

Compositions ophtalmiques contenant du dorzolamide, du timolol et de la brimonidine Download PDF

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Publication number
WO2011027365A9
WO2011027365A9 PCT/IN2010/000591 IN2010000591W WO2011027365A9 WO 2011027365 A9 WO2011027365 A9 WO 2011027365A9 IN 2010000591 W IN2010000591 W IN 2010000591W WO 2011027365 A9 WO2011027365 A9 WO 2011027365A9
Authority
WO
WIPO (PCT)
Prior art keywords
composition
brimonidine
timolol
dorzolamide
hydroxyethyl cellulose
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/IN2010/000591
Other languages
English (en)
Other versions
WO2011027365A3 (fr
WO2011027365A2 (fr
Inventor
Rajesh Kshirsagar
Chandrashekar Kadam
Ajay Mhaske
Sm Mudda
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.)
Micro Labs Ltd
Original Assignee
Micro Labs Ltd
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 Micro Labs Ltd filed Critical Micro Labs Ltd
Priority to RU2012113380/15A priority Critical patent/RU2012113380A/ru
Publication of WO2011027365A2 publication Critical patent/WO2011027365A2/fr
Publication of WO2011027365A9 publication Critical patent/WO2011027365A9/fr
Publication of WO2011027365A3 publication Critical patent/WO2011027365A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • 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
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • 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
    • A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
    • A61K31/382—Heterocyclic compounds having sulfur as a ring hetero atom having six-membered rings, e.g. thioxanthenes
    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/498—Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
    • 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
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • 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
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • 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
    • A61K9/0048—Eye, e.g. artificial tears

Definitions

  • the present invention is related to ophthalmic composition comprising Dorzolamide, Timolol and Brimonidine. More specifically, the present invention is related to stable ophthalmic composition comprising Dorzolamide, Timolol, Brimonidine and hydroxyethyl cellulose.
  • actives may not compatible with each other and with excipients and may not be stable formulations for prolonged period of time.
  • Solubility actives may have different solubility profile and may not be soluble in solvent system suitable for one active. In this case one of the active may get crystallized from formulation immediately or on prolonged storage.
  • Viscosity the viscosity is critical for ophthalmic products as it determines dose to be instilled based on drop size of the formulations, while combining more than one active in same ophthalmic formulation the required viscosity and hence drop size may not be achieved.
  • Container in-compatibility When more than one active are present in one ophthalmic formulation then one of the active may not stable in specific polymer grade used to manufacture container this may lead to degradation of active. 6) Storage conditions: When more than one active are present in one ophthalmic formulation one active may require different storage condition than other active.
  • pH One active may be stable at different pH condition while other may be stable at other pH condition.
  • the present invention provides a stable ophthalmic composition comprising Dorzolamide, Timolol and Brimonidine.
  • the present invention further provides an ophthalmic composition comprising Dorzolamide, Timolol and Brimonidine comprising hydroxyethyl cellulose wherein hydroxyethyl cellulose is used as stability enhancer.
  • the present invention further provides an ophthalmic composition comprising Dorzolamide, Timolol and Brimonidine comprising hydroxyethyl cellulose wherein hydroxyethyl cellulose is used as solubility enhancer.
  • Dorzolamide as used in the invention is meant to cover Dorzolamide in the form of freebase or its pharmaceutically acceptable salt(s), hydrate(s), solvate(s) and physiologically functional derivative(s) and precursors thereof.
  • Timolol as used in the invention is meant to cover Timolol in the form of freebase or its pharmaceutically acceptable salt(s), hydrate(s), solvate(s) and physiologically functional derivative(s) and precursors thereof.
  • Brimonidine as used in the invention is meant to cover Brimonidine in the form of freebase or its pharmaceutically acceptable salt(s), hydrate(s), solvate(s) and physiologically functional derivative(s) and precursors thereof. Unless indicated otherwise, all ingredient concentrations are presented in units of % weight/volume (% w/v).
  • HEC Hydroxyethyl Cellulose
  • Hercules Inc. Amin Division
  • a preferred HEC for use in the compositions of the present invention is the NF grade material, which is commercially available as Natrasol 250HX.
  • compositions of the present invention may contain one or more other ingredients as excipients.
  • compositions may include one or more pharmaceutically acceptable buffering agents, preservatives (including is preservative adjuncts), non-ionic tonicity- adjusting agents, surfactants, solubilizing agents, stabilizing agents, comfort-enhancing agents, emollients, pH-adjusting agents.
  • preservatives including is preservative adjuncts
  • non-ionic tonicity- adjusting agents surfactants
  • solubilizing agents stabilizing agents
  • comfort-enhancing agents comfort-enhancing agents
  • emollients pH-adjusting agents.
  • the present inventors have further found that the ophthalmic composition comprising Dorzolamide, Timolol and Brimonidine are more stable for prolonged period of time when hydroxyethyl cellulose is used as solubilizing agent and stabilizing agent in the composition and composition has pH from about 5 to about 7.
  • the present inventors have further found that the ophthalmic composition comprising Dorzolamide, Timolol and Brimonidine are more stable for prolonged period of time when hydroxyethyl cellulose has viscosity from about 40 cps to about 200 cps.
  • the various embodiments of the present invention can be assembled in several different ways.
  • the present invention provides an ophthalmic composition
  • ophthalmic composition comprising Dorzolamide, Timolol and Brimonidine, which is physicochemically compatible and stable.
  • the present invention provides an ophthalmic composition comprising Dorzolamide, Timolol and Brimonidine wherein Dorzolamide is in solubilized form.
  • the present invention provides an ophthalmic composition comprising Dorzolamide, Timolol and Brimonidine wherein Brimonidine is in solubilized form.
  • the present invention provides an ophthalmic composition
  • ophthalmic composition comprising Dorzolamide (2%w/v), Timolol (0.5%w/v) and Brimonidine (0.2%w/v), hydroxyethyl cellulose and one or more excipients.
  • the present invention provides an ophthalmic composition comprising Dorzolamide, Timolol and Brimonidine wherein composition comprises of hydroxyethyl cellulose wherein hydroxyethyl cellulose used as solubility enhancer and one or more excipients.
  • the present invention provides a stabilized ophthalmic composition comprising Dorzolamide, Timolol and Brimonidine wherein composition further comprises of hydroxyethyl cellulose used as stability enhancer and one or more excipients.
  • the present invention provides a stabilized ophthalmic composition
  • a stabilized ophthalmic composition comprising Dorzolamide, Timolol and Brimonidine wherein composition comprises of hydroxyethyl cellulose wherein the composition is packed in LDPE container.
  • the present invention provides a stabilized ophthalmic composition
  • a stabilized ophthalmic composition comprising Dorzolamide, Timolol and Brimonidine comprising hydroxyethyl cellulose wherein the pH of composition is from about 5 to about 7, preferably about 5.5 to 6.5.
  • the present invention provides a stabilized ophthalmic composition
  • a stabilized ophthalmic composition comprising Dorzolamide, Timolol and Brimonidine comprising hydroxyethyl cellulose wherein the viscosity of the composition is from about 20 cps to about 120 cps.
  • the present invention provides a stabilized ophthalmic composition
  • a stabilized ophthalmic composition comprising Dorzolamide, Timolol and Brimonidine comprising hydroxyethyl cellulose having viscosity from about 40cps to about 200cps, preferably 60cps to 120cps.
  • the present invention provides a stabilized ophthalmic composition
  • a stabilized ophthalmic composition comprising Dorzolamide, Timolol and Brimonidine wherein composition comprises of hydroxyethyl cellulose wherein the compositioa is stable for more than six months, still preferably more than twelve months.
  • the present invention provides an ophthalmic composition
  • an ophthalmic composition comprising Dorzolamide, Timolol and Brimonidine and hydroxyethyl cellulose wherein hydroxyethyl cellulose is present from about 0.1 % w/v to about 1 % w/v of the composition, preferably from about 0.2% w/v to about 0.8 % w/v of the composition, still preferably from about 0.3% w/v to about 0.6% w/v of the composition.
  • the present invention provides an ophthalmic composition comprising Dorzolamide, Timolol and Brimonidine and hydroxyethyl cellulose wherein drop size of ophthalmic composition is from about 35 ⁇ to about 45 ⁇ , still preferably 40 ⁇ .
  • the present invention provides a process of preparing ophthalmic composition comprising Dorzolamide, Timolol and Brimonidine , hydroxyethyl cellulose and one or more pharmaceutically acceptable excipients.
  • the present invention provides an ophthalmic composition
  • an ophthalmic composition comprising: a) Dorzolamide - 2% w/v
  • the present invention consists of a qualitative composition as well as a novel quantitative composition for the treatment of ocular hypertension containing a combination of Dorzolamide, Timolol and Brimonidine, with excipients such as hydroxyethyl cellulose, which allow for the co-existence of the three active principles with good stability.
  • Example 1 The invention will be further illustrated by the following examples, which are intended to be illustrative but not limiting.
  • Example 1
  • a formulation as shown in table 1 was prepared as follows:

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • General Chemical & Material Sciences (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Inorganic Chemistry (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Wind Motors (AREA)

Abstract

La présente invention concerne une composition ophtalmique comprenant du timolol, du dorzolamide et de la brimonidine. Plus spécifiquement, la présente invention concerne une composition ophtalmique stable comprenant du timolol, du dorzolamide et de la brimonidine, y compris de l'hydroxyéthyl cellulose.
PCT/IN2010/000591 2009-09-07 2010-09-03 Compositions ophtalmiques contenant du dorzolamide, du timolol et de la brimonidine Ceased WO2011027365A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
RU2012113380/15A RU2012113380A (ru) 2009-09-07 2010-09-03 Офтальмологические композиции, содержащие дорзоламид, тимолол и бримонидин

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN2151/CHE/2009 2009-09-07
IN2151CH2009 2009-09-07

Publications (3)

Publication Number Publication Date
WO2011027365A2 WO2011027365A2 (fr) 2011-03-10
WO2011027365A9 true WO2011027365A9 (fr) 2011-04-14
WO2011027365A3 WO2011027365A3 (fr) 2011-06-23

Family

ID=43429374

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IN2010/000591 Ceased WO2011027365A2 (fr) 2009-09-07 2010-09-03 Compositions ophtalmiques contenant du dorzolamide, du timolol et de la brimonidine

Country Status (2)

Country Link
RU (1) RU2012113380A (fr)
WO (1) WO2011027365A2 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108601763A (zh) * 2016-02-22 2018-09-28 参天制药株式会社 含有多佐胺和溴莫尼定的药物组合物

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10517869B2 (en) 2013-12-24 2019-12-31 Sentiss Pharma Private Limited Topical brimonidine tartrate ophthalmic solution

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008027340A2 (fr) * 2006-08-30 2008-03-06 Merck & Co., Inc. Formulations ophtalmiques locales
MX2007010025A (es) 2007-08-17 2009-02-25 Arturo Jimenez Bayardo Composición farmacéutica para tratamiento de hipertensión ocular.
MX2007011165A (es) 2007-09-12 2009-03-11 Arturo Jimenez Bayardo Composición farmacéutica estable de timolol, dorzolamida y brimonidina.

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108601763A (zh) * 2016-02-22 2018-09-28 参天制药株式会社 含有多佐胺和溴莫尼定的药物组合物
RU2745317C2 (ru) * 2016-02-22 2021-03-23 Сантен Фармасьютикал Ко., Лтд. Фармацевтическая композиция, включающая дорзоламид и бримонидин
CN113476449A (zh) * 2016-02-22 2021-10-08 参天制药株式会社 含有多佐胺和溴莫尼定的药物组合物

Also Published As

Publication number Publication date
WO2011027365A3 (fr) 2011-06-23
WO2011027365A2 (fr) 2011-03-10
RU2012113380A (ru) 2013-10-20

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