Planta piloto de Producción de Medicamentos, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 570, 2000, Rosario, Argentina.
Área Análisis de Medicamentos, Departamento Química Orgánica, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 570, 2000, Rosario, Argentina.
AAPS PharmSciTech. 2018 May;19(4):1781-1788. doi: 10.1208/s12249-018-0992-5. Epub 2018 Mar 30.
Liquid formulations can be used in children of different ages by varying the volume of the administered dose in order to ensure an exact dosage. The aim of this work was to develop and to optimize a safe liquid atenolol formulation and to carry out the corresponding chemical and microbiological stability studies. A Plackett-Burman design was used to determine the factors that could be critical in the development of the formulations, and a central composite design was used to determine the optimal working conditions. As a result of these analyses, three formulations were selected and their stability studied in three storage conditions, 4, 25, and 40°C. After 6 months of stability testing, the optimal systems showed no pH change or atenolol loss; however, only glycerin-based formulations showed no microbial development. These systems, employing excipients in a range that the EMA has recommended, showed chemical and microbiological stability for at least 6 months even at the worst storage conditions.
液体剂型可通过改变给药剂量的体积来用于不同年龄段的儿童，以确保准确的剂量。本工作的目的是开发和优化安全的液体阿替洛尔制剂，并进行相应的化学和微生物稳定性研究。采用 Plackett-Burman 设计来确定可能对制剂开发至关重要的因素，采用中心复合设计来确定最佳工作条件。通过这些分析，选择了三种制剂，并在 4、25 和 40°C 三种储存条件下研究其稳定性。经过 6 个月的稳定性测试，最佳系统没有显示 pH 值变化或阿替洛尔损失；然而，只有基于甘油的制剂没有显示微生物生长。这些系统使用 EMA 推荐的范围内的赋形剂，即使在最恶劣的储存条件下，也至少能保持 6 个月的化学和微生物稳定性。
