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WO2011027365A9 - Ophthalmic compositions containing dorzolamide, timolol and brimonidine - Google Patents

Ophthalmic compositions containing dorzolamide, timolol and 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
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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
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French (fr)
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WO2011027365A2 (en
WO2011027365A3 (en
Inventor
Rajesh Kshirsagar
Chandrashekar Kadam
Ajay Mhaske
Sm Mudda
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Micro Labs Ltd
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Micro Labs Ltd
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Filing date
Publication date
Application filed by Micro Labs Ltd filed Critical Micro Labs Ltd
Priority to RU2012113380/15A priority Critical patent/RU2012113380A/en
Publication of WO2011027365A2 publication Critical patent/WO2011027365A2/en
Publication of WO2011027365A9 publication Critical patent/WO2011027365A9/en
Publication of WO2011027365A3 publication Critical patent/WO2011027365A3/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • 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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  • Pharmacology & Pharmacy (AREA)
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  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Ophthalmology & Optometry (AREA)
  • Inorganic Chemistry (AREA)
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Abstract

The present invention is related to ophthalmic composition comprising Timolol, Dorzolamide and Brimonidine. More specifically, the present invention is related to a stable ophthalmic composition comprising Timolol, Dorzolamide and Brimonidine and hydroxyethyl cellulose.

Description

OPHTHALMIC COMPOSITIONS CONTAINING PORZOLAMIDE.
TIMOLOL AND BRIMONIDINE
FIELD OF THE INVENTION
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.
BACKGROUND OF THE INVENTION
The combination ophthalmic products are well studied and reported in the state of the art. However ophthalmic formulations containing more than two actives are less studied and reported in the state of the art.
The formulation challenges posed by ophthalmic combination products can be summarized as below;
1) Compatibility: actives may not compatible with each other and with excipients and may not be stable formulations for prolonged period of time. 2) 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.
3) Stability: actives may not be stable in co-presence of each other leading to their degradation and thus instable product. 4) 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.
5) 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.
7) pH: One active may be stable at different pH condition while other may be stable at other pH condition. When the ophthalmic combination product has more than two actives then above-mentioned problems becomes more critical.
The combination of Dorzolamide, Timolol and Brimonidine has proven to have significant advantages over state of the art ocular hypertension agents. United States application no. 2009/0048261 (Tornero Montano et al.) discloses a pharmaceutical composition for the treatment of ocular hypertension comprising combination of Dorzolamide, Timolol and Brimonidine.
To date, only United States application no. 2009/0069345 (Tornero Montano et al.) discloses a pharmaceutical composition comprising Dorzolamide, Timolol and Brimonidine by consisting of the following excipients: Polyoxyl 40 Stearate, Sodium Borate crystals, Sodium Chloride, Mannitol and Benzalkonium chloride. However this application does not teach the stability, solubility and other criticalities for Dorzolamide, Timolol and Brimonidine combination product mentioned earlier.
Thus the combination of Dorzolamide, Timolol and Brimonidine and its formulation criticalities are less studied. Thus there is need in the art for stable and improved formulations comprising combination of Dorzolamide, Timolol and Brimonidine.
SUMMARY OF THE INVENTION:
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.
DETAILED DESCRIPTION OF THE INVENTION
The term "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.
The term "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.
The term "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).
Hydroxyethyl Cellulose (HEC) is commercially available from Hercules Inc. (Aqualon Division) in a variety of grades, including Natrasol 250 L, Natrasol 250 M, Natrasol 250 H, and Natrasol 250 HH. A preferred HEC for use in the compositions of the present invention is the NF grade material, which is commercially available as Natrasol 250HX.
In addition, the compositions of the present invention may contain one or more other ingredients as excipients.
For example, the 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. The present inventors have now found that selection of excipients is critical for development of a stable ophthalmic composition comprising Dorzolamide, Timolol and Brimonidine.
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.
In one embodiment the present invention provides an ophthalmic composition comprising Dorzolamide, Timolol and Brimonidine, which is physicochemically compatible and stable.
In yet another embodiment the present invention provides an ophthalmic composition comprising Dorzolamide, Timolol and Brimonidine wherein Dorzolamide is in solubilized form.
In yet another embodiment the present invention provides an ophthalmic composition comprising Dorzolamide, Timolol and Brimonidine wherein Brimonidine is in solubilized form.
In yet another embodiment the present invention provides an 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.
In yet another embodiment 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. In yet another embodiment 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.
In yet another embodiment the present invention provides a stabilized ophthalmic composition comprising Dorzolamide, Timolol and Brimonidine wherein composition comprises of hydroxyethyl cellulose wherein the composition is packed in LDPE container.
In yet another embodiment the present invention provides 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.
In yet another embodiment the present invention provides 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.
In yet another embodiment the present invention provides a stabilized ophthalmic composition comprising Dorzolamide, Timolol and Brimonidine comprising hydroxyethyl cellulose having viscosity from about 40cps to about 200cps, preferably 60cps to 120cps.
In yet another embodiment the present invention provides 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.
In yet another embodiment the present invention provides 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.
In yet another embodiment 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 μΙ to about 45 μΙ, still preferably 40 μΙ. In yet another embodiment the present invention provides a process of preparing ophthalmic composition comprising Dorzolamide, Timolol and Brimonidine , hydroxyethyl cellulose and one or more pharmaceutically acceptable excipients.
In yet another embodiment the present invention provides an ophthalmic composition comprising: a) Dorzolamide - 2% w/v
b) Timolol - 0.5% w/v
c) Brimonidine - 0.2% w/v
d) Hydroxyethyl cellulose from about 0.3% w/v to about 0.6% w/v of the composition. e) Benzalkonium chloride
f) Mannitol
g) Sodium citrate
h) Citric acid
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.
The invention will be further illustrated by the following examples, which are intended to be illustrative but not limiting. Example 1
Preparation of composition:
A formulation as shown in table 1 was prepared as follows:
Water for injection collected and purged with nitrogen, approximately in 30% of water for injection Hydroxyethyl cellulose was dissolved with stirring. Further in remaining amount of water for injection Dorzolamide, Benzalkonium chloride, Mannitol, sodium citrate, Brimonidine and Timolol was dissolved gradually. Both the solutions were mixed together to get uniform clear solution. The prepared formulation was filled in 5 ml LDPE containers put on stability at stability conditions and the results obtained are presented in table No. 2, 3.
Figure imgf000008_0001
Figure imgf000009_0001
Figure imgf000010_0001

Claims

1. An ophthalmic composition comprising a) Dorzolamide; b) Timolol; c) Brimonidine; d) hydroxyethyl cellulose; and one or more pharmaceutically acceptable excipients.
2. The composition according to claim 1 wherein Dorzolamide is present 2% w/v of the composition.
3. The composition according to claim 1 wherein Timolol is present 0.5% w/v of the composition.
4. The composition according to claim 1 wherein Brimonidine is present 0.2% w/v of the composition.
5. The composition according to claim 1 wherein hydroxyethyl cellulose is used as stability enhancer.
6. The composition according to claim 1 wherein hydroxyethyl cellulose is used as solubility enhancer.
7. The composition according to claim 1 wherein viscosity of the composition is from about 20 cps to about 120 cps.
8. The composition according to claim 1 wherein composition has pH from about 5 to about 7.
9. The composition according to claim 1 wherein the composition is packed in LDPE container.
10. The composition according to claim 1 wherein the composition is stable for more than six months.
11. The composition according to claim 1 wherein drop size of the composition is from about 35 μΙ to about 45 μΙ.
12. The composition according to claim 1 1 wherein drop size of the composition is 40 μΙ.
13. The composition according to claim 1 wherein hydroxyethyl cellulose has viscosity from about 40 cps to about 200 cps.
14. The composition according to claim 1 wherein the hydroxyethyl cellulose is present from about 0.1 % w/v to about 1 % w/v of the composition.
15. The composition according to claim 14 wherein the hydroxyethyl cellulose is present from about 0.2% w/v to about 0.8% w/v of the composition.
16. The composition according to claim 14 wherein the hydroxyethyl cellulose is present from about 0.3% w/v to about 0.6% w/v of the composition.
17. A method of treating ocular hypertension by using the composition according to claim 1.
18. A process of preparing an ophthalmic composition comprising a) Dorzolamide; b) Timolol; c) Brimonidine; d) Hydroxyethyl cellulose; and one or more pharmaceutically acceptable excipients.
19. An ophthalmic composition comprising: a) Dorzolamide - 2% w/v b) Timolol - 0.5% w/v c) Brimonidine - 0.2% w/v d) Hydroxyethyl cellulose - from about 0.3% w/v to about 0.6% w/v e) Benzalkonium chloride f) Mannitol g) Sodium citrate h) Citric acid
20. A process of preparing ophthalmic composition according to claim 19.
21. The composition according to claim 19 wherein viscosity of the composition is from about 20 cps to about 120 cps.
22. An ophthalmic composition according to claim 19 wherein composition has pH from about 5 to about 7.
PCT/IN2010/000591 2009-09-07 2010-09-03 Ophthalmic compositions containing dorzolamide, timolol and brimonidine Ceased WO2011027365A2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
RU2012113380/15A RU2012113380A (en) 2009-09-07 2010-09-03 OPHTHALMIC COMPOSITIONS CONTAINING DORZOLAMIDE, THYMOL AND BRIMONIDINE

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

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108601763A (en) * 2016-02-22 2018-09-28 参天制药株式会社 Pharmaceutical composition containing Dorzolamide and Brimonidine

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3086776B1 (en) * 2013-12-24 2020-06-17 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 (en) * 2006-08-30 2008-03-06 Merck & Co., Inc. Topical ophthalmic formulations
MX2007010025A (en) 2007-08-17 2009-02-25 Arturo Jimenez Bayardo Pharmaceutical composition for treatment of ocular hypertension.
MX2007011165A (en) 2007-09-12 2009-03-11 Arturo Jimenez Bayardo Pharmaceutically stable compound consisting of timolol, dorzolamide and brimonidine.

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108601763A (en) * 2016-02-22 2018-09-28 参天制药株式会社 Pharmaceutical composition containing Dorzolamide and Brimonidine
RU2745317C2 (en) * 2016-02-22 2021-03-23 Сантен Фармасьютикал Ко., Лтд. Pharmaceutical composition including dorsolamide and brimonidine
CN113476449A (en) * 2016-02-22 2021-10-08 参天制药株式会社 Pharmaceutical composition containing dorzolamide and brimonidine

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