Stability and compatibility of drug mixtures in an implantable infusion system

Abstract

SummaryThis study evaluated the stability and the compatibility of mixtures of morphine sulphate, bupivacaine, and clonidine hydrochloride and of hydromorphone, bupivacaine, and clonidine hydrochloride, when used in constant flow implantable pumps under simulated clinical use conditions. The pumps were filled with drug mixtures and incubated at 37°C for a period of 90 days. Aliquots were sampled monthly from the reservoir and catheter outlet and the drug concentrations analysed using validated chromatography methods. Individual materials from the infusion system were immersed in the drug mixtures and stored at 37°C for 60 weeks and evaluated for mechanical performance for compatibility testing. Both drug mixtures were found to be stable over 90 days in the pump at 37°C. All device materials retained acceptable mechanical performance following exposure. These results demonstrate that both drug mixtures are stable when maintained at simulated body temperature in an implantable infusion system for 90 days.

Polyanalgesic Consensus Conference 2012: Recommendations for the Management of Pain by Intrathecal (Intraspinal) Drug Delivery: Report of an Interdisciplinary Expert Panel

“…Although few studies have been conducted to evaluate the stability of combinations of two or more drugs, (269–273) in clinical experience, patient response to IT polytherapy is often suggestive of stability. Postinfusion quantitative analysis on random samples has revealed drug stability, but more studies are necessary (274,275).…”

Stability and Tolerability of High Concentrations of Intrathecal Bupivacaine and Opioid Mixtures in Chronic Noncancer Pain: An Open-Label Pilot Study

“…Another simulated study using 7.5 mg/mL bupivacaine in aqueous hyperbaric dextrose (82.5 mg/mL) showed a similar bupivacaine stability with greater than 96% of the original concentration remaining at 12 weeks [18]. A recent in vitro study that examined mixtures of morphine sulphate or hydromorphone (both 50 mg/mL), bupivacaine hydrochloride (24 mg/mL), and clonidine hydrochloride (2 mg/mL) showed good stability over 90 days at 37°C [19]. These laboratory reports support our in vivo results and confirm the stability of bupivacaine when mixed with morphine or hydromorphone for intrathecal delivery.…”

Advancing Safety in Intrathecal Analgesia

“…13,14,16 In addition, the ITPD is programmed to integrate ingredient solubility, stability, conversion factors for salt formulations, isotonicity, and aliquots to correct for measurements lower than current equipment capabilities. 6,[17][18][19][20] Finally, cost of ingredients for charges is calculated based on availability of medication options and pharmacy location as appropriate. After review by a second pharmacist, the Master Formulation and Compounding Record, including compounding instructions, may be printed for use during the compounding workflow process, after which it can be uploaded into the ITPD and the Medical Center's electronic medical record system.…”