Captopril oral solution for pediatric use: formulation, stability study and palatability assessment in vivo

Abstract The aim of this work was to develop an oral solution of captopril at 5 mg/mL preservative-free. Two formulations were prepared, one containing sweetener (formulation 1) and the other without this excipient (formulation 2). The results found of validation parameters from analytical method performed by HPLC for captopril were, linearity 0.9998, the limit of detection 15.71 µg/mL, the limit of quantification 47.60 µg/mL, repeatability 1.05%, intermediate precision 2.42%, accuracy intraday 101,53%, accuracy inter-day 99.85%. Moreover, the results found for captopril disulfide were, linearity 0.9999, limit of detection 0.65 µg/mL, limit of quantification 1.96 µg/mL, repeatability 2.28%, intermediate precision 1.51%, accuracy intraday 101.36%, accuracy inter-day 100.29%. The appearance of formulations was clear and colorless, pH measures were 3.12 and 3.04, dosage of captopril and captopril disulfide were 99.45% and 99.82%, 0.24% and 0.12% for formulation 1 and formulation 2, respectively. The stability study demonstrated that the concentration of captopril and captopril disulfide in the formulations was > 90% and below 3%, respectively. The in vivo palatability study in animals and humans showed that Formulation 1 containing the sweetener had better acceptance. Thus, the sweetener was able to improve the unpleasant taste of the formulation.

摘要 本研究旨在开发浓度为5 mg/mL的无防腐剂卡托普利（captopril）口服溶液。共制备两种处方：处方1添加甜味剂，处方2不含该药用辅料。采用高效液相色谱法（High Performance Liquid Chromatography，HPLC）对卡托普利进行分析方法学验证，所得参数结果如下：线性相关系数为0.9998，检出限为15.71 µg/mL，定量限为47.60 µg/mL，重复性为1.05%，中间精密度为2.42%，日内准确度为101.53%，日间准确度为99.85%。针对卡托普利二硫化物（captopril disulfide）的验证结果为：线性相关系数0.9999，检出限0.65 µg/mL，定量限1.96 µg/mL，重复性2.28%，中间精密度1.51%，日内准确度101.36%，日间准确度100.29%。两种处方制剂外观均为无色澄清液体，pH值分别为3.12和3.04；处方1与处方2的卡托普利含量分别为99.45%、99.82%，卡托普利二硫化物含量分别为0.24%、0.12%。稳定性研究结果显示，两种处方中卡托普利浓度均保持在90%以上，卡托普利二硫化物含量均低于3%。动物与人体体内适口性评价结果表明，添加甜味剂的处方1具有更佳的接受度，甜味剂可有效改善制剂的不良口感。