Physico-chemical stability of infusion solutions for epidural administration containing fentanyl and bupivacaine or lidocaine.
This study examines the physico-chemical stability of infusion solutions for epidural administration containing bupivacaine hydrochloride 0.06% or 0.125% or lidocaine hydrochloride 0.25% in 0.9% sodium chloride, each with fentanyl 0.0002%. The solutions were prepared in polyvinyl chloride (PVC) infusion bags and stored without overwrap at room temperature (25-30 degrees C) or refrigerated (4-8 degrees C). Over a period of 32 days stability was determined by visual inspection, pH measurement, and HPLC assay of drug concentrations. Admixtures of bupivacaine/fentanyl and lidocaine/fentanyl proved to be chemically stable over a 32 day period, but physical incompatibility (sorption) with PVC-bags was discovered. The stability of the admixtures was influenced by pH and storage temperature. In none of the tested admixtures with an initial pH value lower than 6, did the concentrations of fentanyl or the local anesthetic decrease under 90% of the initial concentrations. A solution of fentanyl and lidocaine with an initial pH of 6.7 exhibited a rapid decrease of drug concentrations. Supposing fentanyl loss was due to sorption, buffered single drug fentanyl solutions of pH 5.5, 5.8, 6.3, and 6.7 were prepared in glass and PVC containers and stored under the same conditions. All solutions in PVC bags showed relevant fentanyl loss which was more evident at higher pH, whereas fentanyl concentration remained unchanged in glass containers at any of the tested pH values.
Apotheke Klinikum, Johannes Gutenberg-Universität Mainz, Germany.
A
A
Sattler
J
J
Jage
I
I
Krämer
D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000737:chemistry*; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000737:chemistry*; D002045:Bupivacaine / Q000008:administration & dosage / Q000737:chemistry*; D002138:Calibration; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D004349:Drug Packaging; D004355:Drug Stability; D005283:Fentanyl / Q000008:administration & dosage / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007202:Indicators and Reagents; D007262:Infusions, Intravenous; D007268:Injections, Epidural; D008012:Lidocaine / Q000008:administration & dosage / Q000737:chemistry*; D019999:Pharmaceutical Solutions; D013056:Spectrophotometry, Ultraviolet
D000701:Analgesics, Opioid; D000779:Anesthetics, Local; D007202:Indicators and Reagents; D019999:Pharmaceutical Solutions; D008012:Lidocaine; D005283:Fentanyl; D002045:Bupivacaine