| Summary: | 碩士 === 國立臺灣大學 === 臨床藥學研究所 === 90 === Captopril, an angiotensin converting enzyme inhibitor, is often used to treat hypertension and congestive heart failure in pediatric patients. Because there is no suitable dosage form of captopril for pediatric use, providing compounding service for divided powders for pediatric patients has been considered as a required service in most of the health care institutions in Taiwan.
Through this study, stability studies of captopril solution would be used to evaluate the plausibility of clinical use of extemporaneously prepared oral captopril solution. The aim is to establish an accurate procedure and beyond-use date of captopril solution to provide an effective and safe extemporaneous preparation for pediatric patients.
This study was designed to investigate factors that may affect the stability of captopril solution, such as solvent, storage temperature and light. Therefore, there were eight combinations of different captopril solution preparations and storage conditions using a 23 factorial study design. Captopril aqueous solutions of 1 mg/mL or 0.5 mg/mL were prepared and stored in plastic bottles at 4℃ or 25℃, and protected from light or not based on the study design. Samples were taken out from these storage conditions after 0, 1, 3, 5, 7, 10, 14, 21 and 28 days to assay captopril and captopril disulfide contents by a stability-indicating high performance liquid chromatography method. Physical and microbiological stabilities were also evaluated during study period.
The results of study revealed that captopril contents in samples stored in the refrigerator and protected from light were higher than 90 % for 14 to 28 days, and relative content of captopril disulfide in most samples were lower than 3 %. The appearance and odor of captopril solutions were recorded, and the results showed that samples were physically stable under a refrigerator condition during storage period. The captopril solutions was microbiologically stable for 28 days when refrigerated, and for 10 days when stored at 25℃. To summarize, captopril solutions stored in tightly closed container and in the refrigerator were stable for 10 days. A conservative “beyond-use date” of 7 days was suggested when captopril solution was used clinically.
In order to simulate the patients or their family members while preparing captopril solution at home, a study was designed to observe the variation of the preparations. The variation of preparing solutions was evaluated through pouring water into a graduated plastic bottle up to the 50-mL scale. Eleven people had participated in this study. The results indicated that intra-subject or inter-subject variations were found to be lower than 2 %. The variation of sampling volume was also evaluated through pouring 5-mL water in a graduated plastic cup. Fifteen people had participated in this study. It was found that the intra-subject variations were 1.86 to 10.03 % and the inter-subject variation was 4.77 %.
From this study, it is concluded that captopril solution is easily prepared and stored. In conjunction with an appropriate and clear patient education about the accurate preparation and measuring procedure for captopril solution, the design from the study can be applied clinically for pediatric patient usage. Most importantly, captopril solution should be refrigerated to ensure its stability. This study also provides an evaluation model for quality assurance for pharmacy practice.
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