Pharmacy Department, Institut de Cancérologie de l'Ouest Paul Papin, Angers, France.
Pharmacy Department, Institut de Cancérologie de l'Ouest Paul Papin, Angers, France.
Neuromodulation. 2023 Aug;26(6):1195-1207. doi: 10.1016/j.neurom.2022.07.008. Epub 2022 Aug 26.
Spinal analgesia is recommended for intractable cancer pain. Morphine-clonidine and sufentanil-clonidine are often used in association in intrathecal drug delivery systems, injected by intraabdominal pumps. To refill these pumps and to limit patient transport, it may be necessary to ship the mixtures in polypropylene syringes to peripheral establishments located near patient homes. The purpose of this study is to determine the stability of morphine-clonidine and sufentanil-clonidine mixtures in polypropylene syringes to ensure the best and safest transport conditions and in implantable pumps for intrathecal use.
The stability study method was conceived according to the International Council for Harmonization guidelines. For polypropylene syringes, four different mixtures of morphine-clonidine and sufentanil-clonidine were assessed over seven days. Two storage temperatures were tested (5 ± 3 °C and 25 ± 2 °C). For implantable pumps, two different mixtures of morphine-clonidine and sufentanil-clonidine were assessed over 28 days and stored at 37 °C.
For the morphine-clonidine mixtures in polypropylene syringes, all mixtures remained stable for five days in both storage conditions (5 ± 3 °C and 25 ± 2 °C) because of relative concentrations systematically positioned between 90% and 110% (95% CIs of the mean of three samples). The two mixtures in implantable pumps remained stable for 28 days. For the sufentanil-clonidine mixtures in polypropylene syringes, cold conservation kept all the preparations stable for seven days, whereas a quick degradation was observed after only two days for ambient storage conditions. This result is similar to that with an implantable pump, in which the concentration is <90% on day 7 for low concentration mixtures. No visual modification, no significant pH modification, and no changes in turbidity assays were observed in either study.
This study shows the stability of the morphine-clonidine mixtures in syringes stored at 5 °C for five days and in implantable pumps stored at 37 °C for 28 days. For the sufentanil-clonidine mixtures, the results show stability in syringes for seven days at 5 °C. Pump results show stability of seven days for low concentrations and 28 days for high concentrations.
椎管内镇痛被推荐用于治疗顽固性癌痛。吗啡-可乐定和舒芬太尼-可乐定经常联合用于鞘内药物输注系统中，通过腹腔内泵注入。为了给这些泵补充药物并限制患者的运输，可能需要将混合物装在聚丙烯注射器中，通过快递寄送到靠近患者家庭的周边机构。本研究的目的是确定吗啡-可乐定和舒芬太尼-可乐定混合物在聚丙烯注射器中的稳定性，以确保最佳和最安全的运输条件，并确保在鞘内使用的植入式泵中保持稳定。
根据国际协调理事会的指导方针，设计了稳定性研究方法。对于聚丙烯注射器，评估了四种不同的吗啡-可乐定和舒芬太尼-可乐定混合物在七天内的稳定性。测试了两种储存温度（5 ± 3°C 和 25 ± 2°C）。对于植入式泵，评估了两种不同的吗啡-可乐定和舒芬太尼-可乐定混合物在 28 天内的稳定性，并在 37°C 下储存。
对于聚丙烯注射器中的吗啡-可乐定混合物，在两种储存条件下（5 ± 3°C 和 25 ± 2°C），所有混合物在五天内都保持稳定，因为相对浓度始终保持在 90%至 110%之间（三个样本平均值的 95%置信区间）。两种混合物在植入式泵中都能稳定 28 天。对于聚丙烯注射器中的舒芬太尼-可乐定混合物，低温保存使所有制剂在七天内保持稳定，而在常温储存条件下，仅两天后就迅速降解。这一结果与植入式泵相似，在植入式泵中，低浓度混合物在第 7 天的浓度<90%。在这两项研究中，都没有观察到可见的变化、pH 值的显著变化或浊度检测的变化。
本研究表明，吗啡-可乐定混合物在 5°C 下储存 5 天的稳定性，以及在 37°C 下储存 28 天的植入式泵的稳定性。对于舒芬太尼-可乐定混合物，在 5°C 下，在注射器中可以稳定 7 天。泵的结果表明，低浓度的药物可以稳定 7 天，高浓度的药物可以稳定 28 天。
