Estudio de estabilidad de soluciones acuosas de captopril en concentración de 1 mg/ml

Objetivo: Estudiar la estabilidad del captopril en solución oral para aplicación en pediatría. Métodos: Las soluciones se preparan para la concentración de 1 mg/ml a partir del producto químico puro. Se emplean como disolventes tres tipos de aguas: agua de la red, envasada y purificada hervida. También se estudian las soluciones preparadas en jarabe y las que contienen citrato sódico para modificar el pH. Se analiza la influencia de agentes quelantes y antioxidantes. Las soluciones se conservan a temperaturas de 4 y 25 °C en envases de plástico PVC (policloruro de vinilo) translúcido. La toma de muestras se hace a intervalos de tiempo regulares inferiores a treinta días. Se emplea cromatografía líquida de alta resolución para determinar la concentraciones de captopril y captopril disulfuro. Resultados: Las preparaciones con agua purificada hervida son más estables que las preparadas con agua de la red o envasada. Las soluciones que contienen edetato disódico, jarabe, ácido ascórbico, ascorbato sódico y metabisulfito sódico, son menos estables. Conclusiones: El cambio de pH no mejora su estabilidad. Las muestras almacenadas a 4 °C son más estables que las conservadas a 25 °C y presentan menor crecimiento microbiano. Las soluciones de captopril 1 mg/ml, preparadas con agua purificada hervida almacenadas en envase de plástico PVC translúcido y protegidas de la luz, son estables durante 30 días a 4 °C.

Objective: The stability of captopril was studied in several extemporaneously prepared oral liquid formulations for pediatric use. Solutions were prepared at a concentration of 1 mg/ml from the pure chemical product. Material and methods: Captopril 1 mg/ml oral liquid formulations were prepared from powder in three types of water (tap water, mineral water, distilled chemically pure water), in syrup and different chelating and antioxidants agents, and the pH was modified with sodium citrate. The liquids were stored at 4 and 25 °C in PVC plastic containers. Samples were removed at regular intervals of less than thirty days. Captopril and captopril disulfide concentrations were analyzed by high-performance liquid chromatography. Captopril in formulations in which the only vehicle was distilled chemically pure water were more stable than in formulations made either with tap water or with mineral water. Results: The formulations containing edetate disodium, syrup, ascorbic acid, sodium ascorbate, sodium metabisulphite were less stable than those in which the only vehicle was distilled chemically pure water. The change of pH did not improve the formulation stability. The samples stored at 4 °C were much more stable than those stored at 25 °C , and the microbiological quality was much better. Conclusions: Captopril, at a concentration of 1 mg/ml, made with distilled chemically pure water stored in PVC plastic container and protected from light, was stable for 30 days at 4 °C.