Stability of hydroxocobalamin in water for injection as cyanide antidote SUMMARY. Background: Cyanide has been used as an agent for chemical warfare, and today it is also a credible terrorism threat agent. Cyanide poisoning is the first cause of death in victims of smoke inhalation from enclosed space fires. Successful treatment for acute cyanide poisoning depends upon rapid antidotes administration, and fixation of the cyanide ion by antidotes. Hydroxocobalamin seems to be a more appropriate antidote than sodium nitrite for empiric treatment of smoke inhalation and other suspected cyanide intoxication victims in the out-of-hospital setting. Stability of hydroxocobalamin in water for injection at cyanide antidote dose has been studied throughout the time and in four types of containers. Methods: The parenteral solution was prepared by aseptic procedures without terminal sterilization, and according to the United States Pharmacopoeia (USP) specifications. Four types of primary containers were used: glass ampoules, semi-rigid polypropylene bags and vials, and rigid plastic vials made of COC. Hydroxocobalamin content and other parameters from the studied solutions, conserved at 4º C, 25º C and 37º C was carried out using molecular spectrometry, liquid-liquid chromatography and others assays. Results: A 4º C the hydroxocobalamin content in the studied samples was invariable (mean 99,81% ± 0,69%; p = 0,95; n = 7; t = 472 days). Very similar results were obtained for samples at 25º C (mean 100,85% ± 1,79%; p = 0,95; n = 6; t = 353 days). At 37º C there was an small decrease in the ampoules hydroxocobalamin content (mean = 92,87% ± 6,08%; p = 0,95; n = 4; t = 472 days). The solution in polypropylene bags suffered a concentration due to water permeation through the container. Both types of vials had hydroxocobalamin contents in the USP specifications (95-115%). Steam sterilization at 115º C for 30 minutes turned hydroxocobalamin content out of specifications. Conclusion: The parenteral solution of hydroxocobalamin in water for injection at the dose of NBC cyanide antidote, ready to use, is stable at temperature below 25ºC, at least for 15 months. Because of the chemical inertia and physical properties, the polypropylene vials are the more appropriated containers for this parenteral solution, which has to be prepared by aseptic procedures without terminal sterilization.

RESUMENAntecedentes: Los autoinyectables (AI) son dispositivos para administración de medicamentos de urgencia por vía parenteral (i.m.) por el afectado o un compañero. Tienen interés militar en Defensa NBQ para la administración de antídotos contra agentes nerviosos y otros medicamentos de urgencia. Se estiman necesarios cinco nuevos AI que pueden ser fabricados por los Servicios Farmacéuticos de la Defensa, además del que se fabrica en la actualidad. Objetivos: Presentación del Autoinyectable AJP (AI-AJP) y su preparado Autoinyectable de atropina-oxima DEF (AI-AOD), resultantes de la I+D sobre AI en el CEMILFARDEF, y su caracterización. Aplicación de resultados al diseño de cinco nuevos AI de interés en Defensa NBQ. Métodos: Ante la falta de ensayos y criterios de valoración oficiales para AI, se realiza una revisión bibliográfica y un estudio retrospectivo sobre la investigación básica llevada a cabo durante dos décadas en el desarrollo y fabricación del AI-AJP, estableciendo procedimientos de caracterización y evaluación de la calidad farmacéutica y propiedades funcionales en condiciones normales y de estrés. Mediante programas ACAD y ensayos galénicos se diseñan cinco nuevos AI. Resultados: Obtención del AI-AJP y su presentación AI-AOD. Presentación de sus componentes, funcionamiento y resultados del análisis de las variables implicadas en su diseño, producción y control: usabilidad, portabilidad, funcionamiento, fuerzas, inyectabilidad, contenidos, esterilidad, partículas, pirógenos, estabilidad, y resistencia. Se expone el diseño de cinco nuevos AI, a los que son aplicables los resultados obtenidos en este estudio. Conclusión: El Autoinyectable AJP cumple los requisitos exigidos por el estado actual de la ciencia, es seguro en funcionamiento, y robusto en resistencia al estrés estático y dinámico. Es estable y la inyección consistente. Se han diseñado cinco nuevos AI (Atropina, Diazepam, Multicomponentes, Morfina y Epinefrina) necesarios en Defensa NBQ y situaciones de urgencia.PALABRAS CLAVE: Autoinyectables, Antídotos NBQ, Medicamentos de urgencia. Study and characterization of the atropine-oxime autoinjector DEF. Design of new autoinjectors for NBC Defense and other emergency drugs SUMMARY:Background: Autoinjectors (AI) are devices for parenteral administration (im) of emergency medications for self or buddy aid. They have NBC Defence military interest for the administration of antidotes against nerve agents and other emergency medications. It is needed five new AI that can be manufactured by the Spanish Pharmaceutical Services, in addition to the one currently made. Objectives: AJP Autoinjector (AI-AJP) presentation and its military medication Autoinjector of atropine-oxime DEF (AI-AOD), as an I+D process result about AI carry out by the Military Pharmaceutical Services, and its characterization. The results are applied to the design of five new AI for NBC Defense. Methods: In the absence of formal testing and evaluation criteria for these devices, the scientific publications and the experience gained...