Pharmacy, Centre Hospitalier Universitaire de Nancy, Vandoeuvre-lès-Nancy, France
Pharmacy, Centre Hospitalier Universitaire de Nancy, Vandoeuvre-lès-Nancy, France.
Eur J Hosp Pharm. 2022 Jul;29(4):228-230. doi: 10.1136/ejhpharm-2020-002468. Epub 2020 Oct 20.
According to the manufacturers, the concentration of etoposide solutions should not exceed 0.4 mg/mL due to a risk of precipitation. Stability studies at higher concentrations were conducted and notably demonstrated 28 day stability up to 1.75 mg/mL for etoposide solutions in 5% dextrose (D5W). Nevertheless, colleagues report precipitation even at 0.4 mg/mL in their daily practice. The objective of this work was to reassess the physical stability of highly concentrated etoposide solutions in D5W (1.2 mg/mL), over a large number of preparations and under different manufacturing processes.
To study the impact of manufacturing process, etoposide was taken with a spike or a needle and injected in three types of D5W containers (Easyflex, Viaflo and Ecoflac). Forty preparations were made for each container. For half of the preparations, a homogenisation was performed by a syringe rinse. Physical stability was realised by two examiners, with a visual examination searching for the appearance of a precipitate, daily during the first week, then twice a week until day 56.
Hundred and eighteen solutions were clear and colourless. Precipitates were observed for two solutions: one in an Easyflex bag on day 4 and one in an Ecoflac container on day 35.
The physical stability at 1.2 mg/mL in D5W remains validated. Precipitations are rare and concern less than 2% of preparations. The appearance of a precipitate does not seem to be correlated to the kind of container or manufacturing process. A rinse was performed for these two solutions to assess a mechanical pressure effect more important on the solution, which could lead to a higher risk of precipitations. However, this is not observed in our daily practice, especially at lower concentrated solutions. We only recommend using an administration set with an in-line micro-filter as a precaution in case of precipitations.
据制造商称，由于有沉淀的风险，依托泊苷溶液的浓度不应超过 0.4mg/mL。已进行了更高浓度下的稳定性研究，研究结果显著表明，在 5%葡萄糖（D5W）中，依托泊苷溶液的浓度高达 1.75mg/mL 时，28 天内保持稳定。然而，同事们在日常实践中报告称，即使在 0.4mg/mL 时也会发生沉淀。这项工作的目的是重新评估在大量制剂和不同生产工艺下，高浓度依托泊苷溶液在 D5W（1.2mg/mL）中的物理稳定性。
为了研究生产工艺的影响，在三种 D5W 容器（Easyflex、Viaflo 和 Ecoflac）中加入依托泊苷的加药器或注射针，进行研究。每个容器制作 40 个制剂。对于一半的制剂，通过注射器冲洗进行均质化。由两名检验员进行物理稳定性检查，每天在第一周进行目视检查，以寻找沉淀的出现，然后每两周检查一次，直到第 56 天。
118 种溶液清澈无色。两种溶液出现沉淀：一种是在 Easyflex 袋中第 4 天，一种是在 Ecoflac 容器中第 35 天。
在 D5W 中浓度为 1.2mg/mL 时，物理稳定性仍然有效。沉淀很少见，不到 2%的制剂有沉淀。沉淀的出现似乎与容器或生产工艺的类型无关。对这两种溶液进行冲洗以评估溶液的机械压力效应更大，这可能会导致沉淀的风险更高。然而，在我们的日常实践中并没有观察到这种情况，特别是在浓度较低的溶液中。我们仅建议在发生沉淀时，作为预防措施，使用带有在线微滤器的输液器。
