Stability of tramadol with three 5-HT₃ receptor antagonists in polyolefin bags for patient-controlled delivery systems

摘要

Background: Mixing 5-hydroxytryptamine-3 (5-HT₃) receptor antagonists with patient-controlled analgesia (PCA) solutions of tramadol has been shown to decrease the incidence of nausea and vomiting associated with the use of tramadol PCA for postoperative pain. However, such mixtures are not commercially available, and the stability of the drug combinations has not been duly studied. The study aimed to evaluate the stability of tramadol with three 5-HT₃ receptor antagonists in 0.9% sodium chloride injection for PCA administration. Materials and methods: Test samples were prepared by adding 1,000?mg tramadol hydrochloride, 8?mg ondansetron hydrochloride, and 6?mg granisetron hydrochloride or 5?mg tropisetron hydrochloride to 100?mL of 0.9% sodium chloride injection in polyolefin bags. The samples were prepared in triplicates, stored at either 25°C or 4°C for 14 days, and assessed using the following compatibility parameters: precipitation, cloudiness, discoloration, and pH. Chemical stability was also determined using a validated high-pressure liquid chromatography method. Results: All of the mixtures were clear and colorless throughout the initial observation period. No change in the concentration of tramadol hydrochloride occurred with any of the 5-HT₃ receptor antagonists during the 14?days. Similarly, little or no loss of the 5-HT₃ receptor antagonists occurred over the 14-day period. Conclusion: Our results suggest that mixtures of tramadol hydrochloride, ondansetron hydrochloride, granisetron hydrochloride, or tropisetron hydrochloride in 0.9% sodium chloride injection were physically and chemically stable for 14?days when stored in polyolefin bags at both 4°C and 25°C.