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.

1 . (canceled) 
     
     
         2 . Method of preparing an ophthalmic aqueous solution of latanoprost, chemically stable at room temperature, for use in the treatment of ocular ailments; said method comprising the steps of:
 a) solubilizing an analog agent of prostaglandin, such as latanoprost;   b) preparing a vehicle solution; and   c) mixing the solubilized latanoprost and the vehicle solution, and top up the volume to 100 L with purified water, constantly agitating for a predetermined period.   
     
     
         3 . Method of preparing a latanoprost ophthalmic solution according to  claim 2 , in which the solubilization of latanoprost phase comprises the steps of:
 a) placing 5.000 g of latanoprost in a recipient with a sufficient capacity and add 15 L of a solution containing 7.5% of hydroxypropylbetacyclodextrins, 0.7% of monobasic phosphate of monohydrated sodium, 0.6% of dibasic phosphate of anhydrous sodium and 0.2% of sodium hyaluronate, and agitate at 500 to 550 rpm in order to dissolve the latanoprost; and   b) waiting until the above solution is fully dissolved and add 0.005% to 0.02% of benzalkonium chloride, agitating for 5 minutes until the solution is homogenized.   
     
     
         4 . Method of preparing a latanoprost ophthalmic solution according to  claim 2 , in which the preparation of the vehicle solution phase consists of the following steps:
 a) in a stainless steel tank, 70 liters of purified water are poured at 30°+−2° C.;   b) agitation is commenced at between 500 and 550 rpm and is maintained constant during the entire preparation process;   c) 7.5 kg of hydroxypropylbetacyclodextrins are added, while maintaining the agitation for approximately 10 minutes in order to dissolve;   d) 700 g of monobasic phosphate of monohydrated sodium is added and it is left for 5 minutes until fully dissolved;   e) 600 g of dibasic phosphate of anhydrous sodium is added and it is left for 5 minutes until fully dissolved;   f) 30 L of this solution are separated for use in the solubilization of latanoprost phase and for the subsequent rinses, and the rest is added to the following raw materials;   g) 200 g of sodium hyaluronate are added slowly while maintaining the agitation for 25 to 35 minutes; and h) 44 g of benzalkonium chloride (solution at 50%) are added, which have previously been dissolved in purified water, and left for 5 minutes until it is fully integrated.   
     
     
         5 . The method of  claim 2 , in which, after mixing the solution of latanoprost and the vehicle solution, the agitation at 500 to 550 rpm is continued for approximately one hour. 
     
     
         6 . The method of  claim 1 , in which the cyclodextrin is combined with the latanoprost in order to help it to dissolve and in order to protect it from hydrolysis. 
     
     
         7 - 12 . (canceled)