Development of a Combined Solution Formulation of Atropine Sulfate and Obidoxime Chloride for Autoinjector and Evaluation of Its Stability

摘要

Atropine (AT) and oximes, alone or in combination, have been proven greatly valuable therapeutics in the treatment of organophosphates intoxications. An injectable mixture of AT and obidoxime (OB) was formulated for the administration by automatic self-injector. The aqueous single dose solution contained 275 mg obidoxime chloride and 2.5 mg atropine sulfate per 1 mL (220 mg and 2 mg per 0.8 effective dose, respectively). The final solution was sterilized by filtration through a 0.22 μm pore size filter. This more concentrated solution allowed to use a smaller size and lighter weight cartridge. Quality control tests, including assay of the two major compounds were performed separately, using reversed-phase HPLC methods. Besides, the stability test was carried out according to ICH guideline for the accelerated test. The obtained results showed that the proposed formulation is stable over a period of 2 years after preparation.