Physicochemical Stability Study of the Morphine-Ropivacaine-Ziconotide Association in Implantable Pumps for Intrathecal Administration

被引:3
作者
Robert, Julien [1 ]
Sorrieul, Jeremy [1 ]
Dupoiron, Denis [2 ]
Jubier-Hamon, Sabrina [2 ]
Bienfait, Florent [2 ]
Visbecq, Anne [3 ]
Devys, Catherine [1 ]
机构
[1] Inst Cancerol Ouest Paul Papin, Pharm Unit, 15 Rue Boquel, Angers, France
[2] Inst Cancerol Ouest Paul Papin, Anesthesia & Pain Dept, Angers, France
[3] Keocyt Lab, Montrouge, France
来源
NEUROMODULATION | 2023年 / 26卷 / 06期
关键词
Cancer pain; chemical stability; chronic pain; intrathecal drug delivery; ziconotide; ADMIXTURES COMBINING ZICONOTIDE; CHEMICAL-STABILITY; OPEN-LABEL; CLONIDINE HYDROCHLORIDE; NEUROPATHIC PAIN; DELIVERY-SYSTEM; CLINICAL-TRIAL; CANCER PAIN; BUPIVACAINE; INFUSION;
D O I
10.1016/j.neurom.2021.10.002
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Purpose: This study aimed to investigate the physicochemical stability of morphine-ropivacaine-ziconotide mixtures used in intrathecal analgesia. Materials and Methods: Eight mixtures were studied to assess their stability profiles according to the initial drug concentrations used. The solutions obtained were put in implantable pumps and stored at 37 degrees C over a period of 60 days. Assays were performed using ultra high-pressure liquid chromatography. Turbidity and pH were also measured throughout the study. Results: Results confirmed excellent physicochemical stability for morphine and ropivacaine. Concerning ziconotide, three of the eight mixtures did not show any sign of chemical instability: average concentrations remained constant throughout the 60 days. A decrease of the concentration was observed for the five other mixtures. Moreover, the appearance of a degradation product linked to oxidation confirmed the ziconotide degradation. Conclusions: All these results are in favor of a physicochemical stable preparation for three of the mixture profiles when stored in implantable pumps at 37 degrees C up to 60 days. For the five others, the efficacy should decrease over time owing to the degradation of ziconotide. The decrease in kinetics of the ziconotide concentration depends on the mixing profile. One possibility is to adapt the filling intervals according to the profile of the mixture. Finally, the results show the period of stability ensuring maximum analgesic efficacy for the eight mixture profiles studied.
引用
收藏
页码:1179 / 1194
页数:16
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