Method of preparing a latanoprost ophthalmic solution and the resulting solution

Abstract

A method of solubilizing an analog active agent of the prostaglandin F2α, such as latanoprost, is described and a method of preparing an ophthalmic solution of the solubilized latanoprost for the treatment of distinct ocular ailments. This invention also refers to an ophthalmic aqueous solution resulting from the aforementioned method, which is characterized by its chemical stability at room temperature, its safety, and innocuousness and efficiency in the treatment of the patient. The new ophthalmic aqueous solution is distinguished because its pharmaceutical value is found in the handling of a vehicle of easy access that not only permits the solubility of latanoprost, but also promotes its chemical stability and, a greater tolerance of the patient with its ophthalmic application for the treatment of the patient's ailment.

Description

BACKGROUND OF THE INVENTION[0001]1. Field of the Invention[0002]The invention relates to a latanoprost ophthalmic solution and a method of preparing same, which is chemically stable at room temperature, and which offers greater efficiency, safety and performance in the treatment of distinct ailments of the eye.[0003]2. Description of Prior Art[0004]The analogs of the prostaglandins are some of the most recent additions to the list of hypotensive ocular medicines available for the treatment of glaucoma. The main mechanism of action of these agents for the reduction of intraocular pressure is, as has been observed in the performed studies, by means of the increase of the elimination of the aqueous humor by means of the conventional path or uveoscleral path. This mechanism consists of the action of these compounds on specific prostanoid receptors of the ciliary muscles and, furthermore, it favors the biosynthesis of metalloproteins of the uterus, a family of proteins that can attach th...

AI Technical Summary

Benefits of technology

[0015]One important object of the invention is to propose a method of solubilizing latanoprost in order to prepare a new ophthalmic aqueous solution, chemically stable at room temperature, which resolves the inconveniences of the currently available solutions of latanoprost.

[0017]Another principal object of the invention is to provide a new ophthalmic aqueous solution of latanoprost, which resolves the inconveniences of the currently available latanoprost solutions, whose degradation is presented in less time. To this end, a new ophthalmic solution is proposed, whose formula Includes ingredients not contained in other latanoprost ophthalmic solutions, such as cyclodextrins, which due to their own characteristics and in combination with other elements of the formula produce a latanoprost ophthalmic solution, chemically stable at room temperature.

[0020]The inclusion of hydroxypropylbetacyclodextrins together with sodium hyaluronate in a new ophthalmic solution of this invention provides a protective and beneficial environment for the latanoprost molecule, because the active ingredient is housed in the lipophilic cavity of the cyclodextrins and at the same time the hydrophilic surface contributes to the solubility in water, while the sodium hyaluronate covers the formed complex. The interaction of the drug with the hydroxypropylbetacyclodextrins and the sodium hyaluronate results in the reduction of the decomposition, which grants protection to the active labile in an aqueous environment.

[0021]In a preferred embodiment of the invention, the aqueous ophthalmic solution is characterized by including latanoprost at a concentration of 0.005%; a pH damper system that may be selected from boric acid, citric acid, sorbic acid, acetic acid, sodium borate, monobasic sodium phosphate, dibasic sodium phosphate, sodium citrate and sodium acetate, in a range of concentration from 0.001% to 5.0%; one or more agents that increase the viscosity, such as hydroxypropylcellulose, carbooxylmethylcellulose, sulfate chondrointin, formal glycerol, methyldinoglycerol and cyclodextrins, in a concentration ranging from 0.05% to 20.00%; one or more tensoactive agents, moisturizers such as polyoxyl 40 stearate, polysorbate 80, poloxamer and tyloxapol, in concentrations ranging from 0.01% to 20.0%; one or more osmolarity regulating agents such as sodium chloride, sorbitol, manitol and dextrose at a concentration ranging from 0.6% to 1.8%, expressed as chemical equivalents of sodium chloride; one or more preservatives such as benzalkonium chloride, benzetonium chloride, thiomersal, phenylmercury acetate or nitrate, parabens, chlorohexidine gluconate, ethylic alcohol, cetrimide, sodium perborate and chlorobutanol in adequate concentration in order to provide an antimicrobian effect. It may also contain one or more antioxidant agents such as disodic edetate, sodium metabisulfite, sodium bisulfate, acetylcysteine, sodium thiosulfate and thiourea in adequate concentration in order to give the required effect.

Problems solved by technology

However, in the case of latanoprost, and other therapeutic active ingredients insoluble in water, are generally prepared in solutions that present numerous inconveniences, with the most important one being the accelerated degeneration of the active ingredient at room temperature.

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