CHU de Bordeaux, Pôle Produits de Santé, Service Pharmacie à Usage Intérieur, Pessac, France.
University of Bordeaux, Inserm, UMR1034, Biology of Cardiovascular Diseases, Pessac, France.
Am J Health Syst Pharm. 2021 Apr 22;78(9):806-812. doi: 10.1093/ajhp/zxab071.
To investigate the long-term chemical and physical stability of 5-mg/mL acyclovir solution in polypropylene bags stored at 5°C ± 3°C for 2 months in order to determine the feasibility of batch production by a centralized intravenous additive service.
Eight empty 100-mL polypropylene bags (bags A) and 8 empty 250-mL bags (bags B) were respectively filled with 60 mL and 200 mL of 5-mg/mL acyclovir and 0.9% sodium chloride injection (NaCl) under aseptic conditions through a semiautomated manufacturing process and vacuum packed before storage at 5°C ± 3°C. Four bags A and 4 bags B were tested for chemical stability via a stability-indicating high-performance liquid chromatography (HPLC) method immediately after preparation (time 0) and after 7, 14, 21, 28, 35, 42, and 63 days. Samples for microbiological assay were collected on days 0 and 63 from 4 bags A and 4 bags B immediately after breaking the vacuum. Osmolality, pH, and physical stability were assessed by visual examination, Subvisible particle counting was performed on 6 additional bags (3 each of bags A and B).
Mean percentage loss of acyclovir relative to the mean experimental concentration at time 0 was below 5% over the 63-day study period.. No significant differences of pH, no change in color and no precipitate were observed during the study. Subvisible particle counts were compliant with European Pharmacopoeia requirements. Acyclovir solutions remained sterile over the 63 days of the study.
Extemporaneously prepared acyclovir 5 mg/mL solutions in 0.9% NaCl stored in polypropylene bags were chemically and physically stable over 63 days when stored at 5°C ± 3°C.
研究 5mg/ml 阿昔洛韦溶液在 5°C±3°C 下于聚丙稀袋中储存 2 个月的长期化学和物理稳定性，以确定由集中静脉添加剂服务进行批量生产的可行性。
在无菌条件下，通过半自动化生产工艺，分别将 60ml 和 200ml 的 5mg/ml 阿昔洛韦和 0.9%氯化钠注射液（NaCl）装入 8 个无菌 100ml 聚丙稀袋（袋子 A）和 8 个无菌 250ml 袋（袋子 B）中，并进行真空包装，然后在 5°C±3°C 下储存。在制备后立即（时间 0）和 7、14、21、28、35、42 和 63 天后，通过稳定性指示高效液相色谱（HPLC）方法对 4 个袋子 A 和 4 个袋子 B 进行化学稳定性测试。在第 0 天和第 63 天，从 4 个袋子 A 和 4 个袋子 B 中立即收集用于微生物检测的样品，打破真空后。通过目测评估渗透压、pH 值和物理稳定性。对另外 6 个袋子（每个袋子 A 和 B 各 3 个）进行亚可见颗粒计数。
在 63 天的研究期间，与时间 0 的平均实验浓度相比，阿昔洛韦的平均损失百分比低于 5%。在研究过程中，没有观察到 pH 值的显著差异、颜色变化和沉淀。亚可见颗粒计数符合欧洲药典的要求。在研究的 63 天内，阿昔洛韦溶液保持无菌。
在 5°C±3°C 下储存时，0.9%NaCl 中临时制备的 5mg/ml 阿昔洛韦溶液在聚丙稀袋中储存 63 天，化学和物理性质稳定。
