Storage-stable formulation of paracetamol in aqueous solution

摘要

The present invention relates to a method for the production of a formulation that is stable to oxidation and that is based on paracetamol in an aqueous solvent, comprising the steps of (i) dissolving paracetamol in an aqueous solvent comprising an isotonic agent that is sodium chloride and a buffer agent that is sodium citrate, having a temperature between 65° C. and 95° C. and having pH between 5.0 and 6.0 in a reaction vessel, (ii) replacing the remaining air in the vessel by an inert gas, such as nitrogen, and cooling the solution so formed to a temperature below 38° C., (iii) adding cysteine hydrochloride to the solution without mechanical agitation, and (iv) closing the reaction vessel and mechanically agitating the solution in a nitrogen atmosphere. The further relates to a formulation prepared according to the method.

主权项

1. Formulation that is stable to oxidation and hydrolysis, based on paracetamol in an aqueous solvent comprising:
between 0.25% and 2% (w/v) paracetamol, between 0.5% and 0.9% (w/v) sodium chloride, between 0.05% and 0.09% (w/v) monosodium citrate monohydrate, between 0.015% and 0.035% (w/v) cysteine hydrochloride monohydrate, and water for injection, where the final pH of the formulation is between 5.0 and 6.0, and wherein the water for injection is not degassed by bubbling with an inert gas, prepared according to a method comprising in given order the steps of: (i) dissolving paracetamol in an aqueous solvent comprising an isotonic agent that is sodium chloride and a buffer agent that is sodium citrate, having a temperature between 65° C. and 95° C. and having pH between 5.0 and 6.0 in a reaction vessel, (ii) replacing the remaining air in the vessel by an inert gas and cooling the solution so formed to a temperature below 38° C., (iii) adding cysteine hydrochloride to the solution without mechanical agitation, and (iv) closing the reaction vessel and mechanically agitating the solution in a nitrogen atmosphere; wherein for at least 15 months from preparation impurity K<0.05%; impurity F <0.05%, as determined by HPLC at 245 nm.