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BR-102017010943-B1 - Ophthalmic pharmaceutical composition of bimatoprost for the treatment of glaucoma and its respective use.

BR102017010943B1BR 102017010943 B1BR102017010943 B1BR 102017010943B1BR-102017010943-B1

Abstract

The present invention relates to an ophthalmic solution composition containing Bimatoprost 0.03% (0.3 mg/mL) and its respective use, indicated for the reduction of increased intraocular pressure in patients with open-angle glaucoma, closed-angle glaucoma in patients previously submitted to iridotomy, ocular hypertension, and obtained through the reactions of the compounds of the Bimatoprost formulas, according to the formulations disclosed in the descriptive report.

Inventors

  • CÉSAR AUGUSTO GONÇALVES
  • GISELE BADAUY LAURIA SILVA
  • VIVIANE DESIDERI

Assignees

  • BIOTEC BIOLÓGICA INDÚSTRIA FARMACÊUTICA LTDA. - E.P.P

Dates

Publication Date
20260310
Application Date
20170524

Claims (20)

  1. 1) OPHTHALMIC PHARMACEUTICAL COMPOSITION OF BIMATOPROST FOR THE TREATMENT OF GLAUCOMA, characterized by containing: - as active ingredient, 0.01% or 0.03% (w/v) of bimatoprost, - as viscosity agent, 0.05% (w/v) of Hydroxypropylmethylcellulose (Methocel F4M) or 0.15% (w/v) of Sodium Hyaluronate, - as surfactant or solubilizing agent, 0.1% or 0.25% (w/v) of Polysorbate 80 and/or 0.4% (w/v) of Polyethylene Glycol 400 and/or 0.25% (w/v) of Castor Oil, - as tonicity agent, 0.81% or 0.83% (w/v) of sodium chloride, - as buffering agent, 0.268% (w/v) Dibasic Sodium Phosphate Heptahydrate and 0.014% (w/v) Citric Acid Monohydrate, as chelating agent, 0.015% (w/v) Disodium EDTA, as vehicle, q.s.p. 100% water for injection, wherein Sodium Hydroxide and Hydrochloric Acid are added in sufficient quantity to adjust the pH of the composition between 6.8 and 7.8, wherein the composition has a viscosity of 5 to 20 cps, wherein the composition has an osmolarity of 290 to 310 mOsm/kg, and wherein the composition remains a sterile solution for at least 6 months in accelerated stability testing.
  2. 2) Composition according to claim 1, characterized in that it additionally contains, as a preservative, 0.013% (w/v) Benzalkonium Chloride (50% solution) or 0.002% (w/v) Sodium Hydroxymethylglycinate (N-IG) or 0.028% (w/v) Sodium Perborate.
  3. 3) Composition, according to claim 1, characterized by containing: - 0.03% (w/v) Bimatoprost, - 0.05% (w/v) Hydroxypropylmethylcellulose (Methocel F4M), - 0.83% (w/v) Sodium Chloride, - 0.1% (w/v) Polysorbate 80, - 0.268% (w/v) Dibasic Sodium Phosphate Heptahydrate, - 0.014% (w/v) Citric Acid Monohydrate, - 0.015% (w/v) Disodium EDTA, - q.s.p. 100% Water for Injection, wherein Sodium Hydroxide and Hydrochloric Acid are added to the composition in sufficient quantity to adjust the pH of the composition between 6.8 and 7.8, and wherein the composition has a viscosity of 8 20 cps.
  4. 4) Composition, according to claim 1, characterized by containing: - 0.03% (w/v) Bimatoprost, - 0.15% (w/v) Sodium Hyaluronate, - 0.81% (w/v) Sodium Chloride, - 0.1% (w/v) Polysorbate 80, - 0.268% (w/v) Dibasic Sodium Phosphate Heptahydrate, - 0.014% (w/v) Citric Acid Monohydrate, - 0.015% (w/v) Disodium EDTA, - q.s.p. 100% Water for injection, wherein Sodium Hydroxide and Hydrochloric Acid are added to the composition in sufficient quantity to adjust the pH of the composition between 6.8 and 7.8, and wherein the composition has a viscosity of 5 to 15 cps.
  5. 5) Composition, according to claim 1, characterized by containing: - 0.03% (w/v) Bimatoprost, - 0.15% (w/v) Sodium Hyaluronate, - 0.81% (w/v) Sodium Chloride, - 0.25% (w/v) Polysorbate 80, - 0.4% (w/v) Polyethylene Glycol 400, - 0.268% (w/v) Dibasic Sodium Phosphate Heptahydrate, - 0.014% (w/v) Citric Acid Monohydrate, - 0.015% (w/v) Disodium EDTA, - q.s.p. 100% Water for Injection, where Sodium Hydroxide and Hydrochloric Acid are added to the composition in sufficient quantity to adjust the pH of the composition between 6.8 and 7,8, and where the composition has a viscosity of 5 to 15 cps.
  6. 6) Composition, according to claim 1, characterized by containing: - 0.03% (w/v) Bimatoprost, - 0.15% (w/v) Sodium Hyaluronate, - 0.81% (w/v) Sodium Chloride, - 0.25% (w/v) Hydrogenated Castor Oil, - 0.4% (w/v) Polyethylene Glycol 400, - 0.268% (w/v) Dibasic Sodium Phosphate Heptahydrate, - 0.014% (w/v) Citric Acid Monohydrate, - 0.015% (w/v) Disodium EDTA, - q.s.p. 100% Water for Injection, where Sodium Hydroxide and Hydrochloric Acid are added to the composition in sufficient quantity to adjust the pH of the composition between 6.8 to 7.8, and where the composition has a viscosity of 5 to 15 cps.
  7. 7) Composition, according to claim 1, characterized by containing: - 0.03% (w/v) Bimatoprost, - 0.15% (w/v) Sodium Hyaluronate, - 0.81% (w/v) Sodium Chloride, - 0.25% (w/v) Polysorbate 80, - 0.25% (w/v) Hydrogenated Castor Oil, - 0.4% (w/v) Polyethylene Glycol 400, - 0.268% (w/v) Dibasic Sodium Phosphate Heptahydrate, - 0.014% (w/v) Citric Acid Monohydrate, - 0.015% (w/v) Disodium EDTA, - q.s.p. 100% Water for Injection, where Hydroxide is added to the composition Sodium and hydrochloric acid in sufficient quantity to adjust the pH of the composition between 6.8 and 7.8, and where the composition has a viscosity of 5 to 15 cps.
  8. 8) Composition, according to claim 1 or 2, characterized by containing: - 0.03% (w/v) Bimatoprost, - 0.05% (w/v) Hydroxypropylmethylcellulose (Methocel F4M), - 0.83% (w/v) Sodium Chloride, - 0.013% (w/v) Benzalkonium Chloride (50% solution), - 0.1% (w/v) Polysorbate 80, - 0.268% (w/v) Dibasic Sodium Phosphate Heptahydrate, - 0.014% (w/v) Citric Acid Monohydrate, - 0.015% (w/v) Disodium EDTA, - q.s.p. 100% Water for Injection, where Sodium Hydroxide and Hydrochloric Acid are added to the composition. in sufficient quantity to adjust the pH of the composition between 6.8 and 7.8, and where the composition has a viscosity of 8 to 20 cps.
  9. 9) Composition, according to claim 1 or 2, characterized by containing: - 0.03% (w/v) Bimatoprost, - 0.15% (w/v) Sodium Hyaluronate, - 0.81% (w/v) Sodium Chloride, - 0.013% (w/v) Benzalkonium Chloride (50% solution), - 0.1% (w/v) Polysorbate 80, - 0.268% (w/v) Dibasic Sodium Phosphate Heptahydrate, - 0.014% (w/v) Citric Acid Monohydrate, - 0.015% (w/v) Disodium EDTA, - q.s.p. 100% Water for Injection, where Sodium Hydroxide and Hydrochloric Acid are added to the composition in sufficient quantity to adjust the pH of the composition between 6.8 and 7.8, and where the composition has a viscosity of 5 to 15 cps.
  10. 10) Composition, according to claim 1 or 2, characterized by containing: - 0.03% (w/v) Bimatoprost, - 0.15% (w/v) Sodium Hyaluronate, - 0.81% (w/v) Sodium Chloride, - 0.013% (w/v) Benzalkonium Chloride (50% solution), - 0.25% (w/v) Polysorbate 80, - 0.4% (w/v) Polyethylene Glycol 400, - 0.268% (w/v) Dibasic Sodium Phosphate Heptahydrate, - 0.014% (w/v) Citric Acid Monohydrate, - 0.015% (w/v) Disodium EDTA, - q.s.p. 100% Water for Injection, where it is added in The composition consists of Sodium Hydroxide and Hydrochloric Acid in sufficient quantity to adjust the pH of the composition between 6.8 and 7.8, and where the composition has a viscosity of 5 to 15 cps.
  11. 11) Composition according to claim 1 or 2, characterized by containing: - 0.03% (w/v) Bimatoprost, - 0.15% (w/v) Sodium Hyaluronate, - 0.81% (w/v) Sodium Chloride, - 0.002% (w/v) Sodium Hydroxymethylglycinate (N-IG), - 0.25% (w/v) Hydrogenated Castor Oil, - 0.4% (w/v) Polyethylene Glycol 400, - 0.268% (w/v) Dibasic Sodium Phosphate Heptahydrate, - 0.014% (w/v) Citric Acid Monohydrate, - 0.015% (w/v) Disodium EDTA, - q.s.p. 100% Water for Injectable, where Sodium Hydroxide and Hydrochloric Acid are added to the composition in sufficient quantity to adjust the pH of the composition between 6.8 and 7.8, and where the composition has a viscosity of 5 to 15 cps.
  12. 12) Composition, according to claim 1 or 2, characterized by containing: - 0.03% (w/v) Bimatoprost, - 0.15% (w/v) Sodium Hyaluronate, - 0.81% (w/v) Sodium Chloride, - 0.028% (w/v) Sodium Perborate, - 0.25% (w/v) Polysorbate 80, - 0.4% (w/v) Polyethylene Glycol 400, - 0.268% (w/v) Dibasic Sodium Phosphate Heptahydrate, - 0.014% (w/v) Citric Acid Monohydrate, - 0.015% (w/v) Disodium EDTA, - q.s.p. 100% Water for Injection, where Hydroxide is added to the composition. Sodium and hydrochloric acid in sufficient quantity to adjust the pH of the composition between 6.8 and 7.8, and where the composition has a viscosity of 5 to 15 cps.
  13. 13) Composition, according to claim 1, characterized by containing: - 0.01% (w/v) Bimatoprost, - 0.05% (w/v) Hydroxypropylmethylcellulose (Methocel F4M), - 0.83% (w/v) Sodium Chloride, - 0.1% (w/v) Polysorbate 80, - 0.268% (w/v) Dibasic Sodium Phosphate Heptahydrate, - 0.014% (w/v) Citric Acid Monohydrate, - 0.015% (w/v) Disodium EDTA, - q.s.p. 100% Water for injection, wherein Sodium Hydroxide and Hydrochloric Acid are added to the composition in sufficient quantity to adjust the pH of the composition between 6.8 and 7.8, and wherein the composition has a viscosity of 8 to 20 capsules.
  14. 14) Composition, according to claim 1, characterized by containing: - 0.01% (w/v) Bimatoprost, - 0.15% (w/v) Sodium Hyaluronate, - 0.81% (w/v) Sodium Chloride, - 0.1% (w/v) Polysorbate 80, - 0.268% (w/v) Dibasic Sodium Phosphate Heptahydrate, - 0.014% (w/v) Citric Acid Monohydrate, - 0.015% (w/v) Disodium EDTA, - q.s.p. 100% Water for injection, wherein Sodium Hydroxide and Hydrochloric Acid are added to the composition in sufficient quantity to adjust the pH of the composition between 6.8 and 7.8, and wherein the composition has a viscosity of 5 to 15 cps.
  15. 15) Composition, according to claim 1, characterized by containing: - 0.01% (w/v) Bimatoprost, - 0.15% (w/v) Sodium Hyaluronate, - 0.81% (w/v) Sodium Chloride, - 0.25% (w/v) Polysorbate 80, - 0.4% (w/v) Polyethylene Glycol 400, - 0.268% (w/v) Dibasic Sodium Phosphate Heptahydrate, - 0.014% (w/v) Citric Acid Monohydrate, - 0.015% (w/v) Disodium EDTA, - q.s.p. 100% Water for injection, where Sodium Hydroxide and Hydrochloric Acid are added to the composition in sufficient quantity to adjust the pH of the composition between 6.8 and 7,8, and where the composition has a viscosity of 5 to 15 cps.
  16. 16) Composition, according to claim 1, characterized by containing: - 0.01% (w/v) Bimatoprost, - 0.15% (w/v) Sodium Hyaluronate, - 0.81% (w/v) Sodium Chloride, - 0.25% (w/v) Hydrogenated Castor Oil, - 0.4% (w/v) Polyethylene Glycol 400, - 0.268% (w/v) Dibasic Sodium Phosphate Heptahydrate, - 0.014% (w/v) Citric Acid Monohydrate, - 0.015% (w/v) Disodium EDTA, - q.s.p. 100% Water for Injection, where Sodium Hydroxide and Hydrochloric Acid are added to the composition in sufficient quantity to adjust the pH of the composition between 6.8 to 7.8, and where the composition has a viscosity of 5 to 15 cps.
  17. 17) Composition, according to claim 1 or 2, characterized by containing: - 0.01% (w/v) Bimatoprost, - 0.15% (w/v) Sodium Hyaluronate, - 0.81% (w/v) Sodium Chloride, - 0.25% (w/v) Polysorbate 80, - 0.25% (w/v) Hydrogenated Castor Oil, - 0.4% (w/v) Polyethylene Glycol 400, - 0.268% (w/v) Dibasic Sodium Phosphate Heptahydrate, - 0.014% (w/v) Citric Acid Monohydrate, - 0.015% (w/v) Disodium EDTA, - q.s.p. 100% Water for Injection, where it is added to the composition Sodium hydroxide and hydrochloric acid in sufficient quantity to adjust the pH of the composition between 6.8 and 7.8, where the composition has a viscosity of 5 to 15 cps.
  18. 18) Composition according to claim 1 or 2, characterized by containing: - 0.01% (w/v) Bimatoprost, - 0.05% (w/v) Hydroxypropylmethylcellulose (Methocel F4M), - 0.83% (w/v) Sodium Chloride, - 0.013% (w/v) Benzalkonium Chloride (50% solution), - 0.1% (w/v) Polysorbate 80, - 0.268% (w/v) Dibasic Sodium Phosphate Heptahydrate, - 0.014% (w/v) Citric Acid Monohydrate, - 0.015% (w/v) Disodium EDTA, - q.s.p. 100% Water for injection, where Sodium Hydroxide and Citric Acid are added to the composition. Hydrochloric acid in sufficient quantity to adjust the pH of the composition between 6.8 and 7.8, where the composition has a viscosity of 8 to 20 cps.
  19. 19) Composition according to claim 1 or 2, characterized by containing: - 0.01% (w/v) Bimatoprost, - 0.15% (w/v) Sodium Hyaluronate, - 0.81% (w/v) Sodium Chloride, - 0.013% (w/v) Benzalkonium Chloride (50% solution), - 0.1% (w/v) Polysorbate 80, - 0.268% (w/v) Dibasic Sodium Phosphate Heptahydrate, - 0.014% (w/v) Citric Acid Monohydrate, - 0.015% (w/v) Disodium EDTA, - q.s.p. 100% Water for Injection, where Sodium Hydroxide and Hydrochloric Acid are added to the composition in sufficient quantity to adjust the pH. The composition has a density between 6.8 and 7.8, and a viscosity of 5 to 15 cps.
  20. 20) Composition, according to claim 1 or 2, characterized by containing: - 0.01% (w/v) Bimatoprost, - 0.15% (w/v) Sodium Hyaluronate, - 0.81% (w/v) Sodium Chloride, - 0.013% (w/v) Benzalkonium Chloride (50% solution), - 0.25% (w/v) Polysorbate 80, - 0.4% (w/v) Polyethylene Glycol 400, - 0.268% (w/v) Dibasic Sodium Phosphate Heptahydrate, - 0.014% (w/v) Citric Acid Monohydrate, - 0.015% (w/v) Disodium EDTA, - q.s.p. 100% Water for Injection, where it is added in The composition consists of Sodium Hydroxide and Hydrochloric Acid in sufficient quantity to adjust the pH of the composition between 6.8 and 7.8, and where the composition has a viscosity of 5 to 15 cps.

Description

TECHNICAL FIELD OF DEVELOPMENT [001] This patent application relates to an ophthalmic solution composition containing Bimatoprost 0.03% (0.3 mg/mL) indicated for the reduction of increased intraocular pressure in patients with open-angle glaucoma, closed-angle glaucoma in patients who have previously undergone iridotomy, and ocular hypertension. [002] It is related to pharmaceutical compositions that contain concentrations of polymers that promote sufficient viscosity to maintain a longer residence time in the conjunctival sac and to pharmaceutical compositions that contain concentrations of surfactants that promote the bioavailability of a therapeutic agent in the composition. [003] More specifically, the present patent application relates to pharmaceutical compositions (e.g., ophthalmic multidose compositions) with relatively low concentrations of surfactants that promote the bioavailability of a therapeutic agent (e.g., a prostaglandin such as Bimatoprost). [004] This patent application relates to the provision of multi-dose preserved ophthalmic compositions. The compositions possess sufficient antimicrobial activity to meet the USP preservative efficacy requirements as well as similar preservative standards (e.g., EP and JP). The compositions have a multi-dose dispensing device that allows for preservative-free formulation. A multi-dose device designed to administer multiple drops of preservative-free products. The system consists of standard pressure bottles. [005] It relates to pharmaceutical compositions containing concentrations of non-ionic isotonic agents that promote a desired osmolarity for ophthalmic solutions, to pharmaceutical compositions containing concentrations of buffers that contribute to stability by preventing pH changes in ophthalmic solutions, and to pharmaceutical compositions containing concentrations of pH-adjusting agents. [006] This relates to a clear, slightly viscous, stable ophthalmic solution comprising Bimatoprost, which is useful as a therapeutic agent for glaucoma, as the active ingredient. HISTORY AND BACKGROUND OF THE INVENTION [007] Bimatoprost is a synthetic prostamide analogue with ocular hypotensive activity. Its chemical name is (Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(1E,3S)-3-hydroxy-5-phenyl-1-pentenyl]cyclopentyl]-5-N-ethyl-heptenamide. [008] The chemical structure of Bimatoprost is: [009] Bimatoprost is a prostamide marketed for the treatment of glaucoma and ocular hypertension. [010] Processes for the preparation of Bimatoprost are described, for example, in US 2017065610, WO 2011/046569, WO 2010/102078, and BR 11 2013 030973 3. [011] The object of this patent application is to provide formulations with longer residence time in the conjunctival sac, formulations of a mucoadhesive Bimatoprost ophthalmic solution. And stable formulations in bottles with devices for multidose preservative-free formulations. [012] Hydroxypropyl methylcellulose (HPMC), a viscosity-enhancing polymer used in ophthalmic preparations, can be used as an adhesive agent. It is the main polymer used in matrices to control drug release. [013] Bimatoprost-loaded gels were prepared using different polymers, namely w/v Hypromellose and w/v Sodium Hyaluronate. [014] Polysorbate 80, a non-ionic surfactant and emulsifier derived from sorbitol, can be used as a surfactant. Polysorbate 80 is described as an ophthalmic demulcent, an agent that is applied topically to the eye to protect and lubricate the surface of the mucous membrane and relieve dryness and irritation; it is also used as a solubilizer. Polysorbates are polyoxyethylene derivatives of sorbitan esters. [015] PEG 40 hydrogenated castor oil Cremophor RH 40/Kolliphor RH 40 is a derivative of hydrogenated castor oil and ethylene oxide, used as a non-ionic oil-in-water solubilizer and emulsifying agent. Kolliphor RH40 is widely used in self-emulsifying drug delivery systems (SEDDS) or microemulsification systems (SMDDS) in combination with a co-solubilizer and/or co-solvent. Furthermore, Kolliphor RH 40 is nearly tasteless – making it ideal for oral and ophthalmic applications. Non-ionic: These are surfactants that possess uncharged hydrophilic groups attached to a fatty chain. [016] As a preservative for ophthalmic solutions, benzalkonium chloride (BAK) is the most widely used from the point of view of preservative effects. However, while BAK has an excellent preservative effect, it can also cause corneal disturbances when used in high concentrations or during prolonged treatment. Accordingly, when adding BAK to ophthalmic solutions, it is desirable to reduce its concentration as low as possible. [017] Sodium hydroxymethylglycinate (N-IG), which may be included in the formulation, is an amino acid derivative that, due to its antimicrobial activity, is an effective preservative that does not exert a harmful effect on the surface of the eye. It is water-miscible. [018] The chemical compound sodium perborate (PBS) is a sodium salt of perboric