Sterility and concentration of liposomal bupivacaine single‐use vial when used in a multiple‐dose manner

Abstract

Objective: To evaluate the sterility of bupivacaine liposome injectable suspension (Nocita ® ) used in a multiple-dose fashion for 5 days.Study design: Triplicate liposomal bupivacaine vials were stored under two conditions, (1) room temperature (24 C) and (2) refrigerated temperature (5 C). A 3-mL aliquot was withdrawn from each vial daily. Samples were inoculated in tryptic soy broth in triplicate and then incubated for 24 hours at 37 C and subcultured every 48 hours onto blood agar and Sabouraud dextrose agar, respectively. Separate 1.5-mL aliquots of liposomal bupivacaine were centrifuged at 3500 g to separate liposome-encapsulated bupivacaine from the solution. Concentration of unencapsulated bupivacaine was analyzed via highpressure liquid chromatography. Data were analyzed by using mixed effects procedure with multiple comparisons.Sample population: Ten 20-mL vials of bupivacaine liposome injectable suspension stored under two conditions, (1) room temperature (24 C) and(2) refrigerated temperature (5 C). Results: Five days of repeated withdrawal from the single-use vials yielded no bacterial growth. One control vial, which was opened and punctured once on the last day of the experiment, yielded fungal growth of an Aspergillus spp, likely an environmental contaminant. The concentration of free bupivacaine did not significantly differ until the fifth day of sampling. Conclusion: When aseptic technique was used, liposomal bupivacaine remained sterile for 5 days. Concentrations of free bupivacaine were unchanged from baseline for 4 days in both refrigerated and room temperature conditions.Clinical significance: Single-use liposomal bupivacaine vials can be used extralabel in a multiple-dose fashion for up to 4 days when stored either refrigerated or room temperature when sterile technique is used.

The effect of extracorporeal shockwave on liposomal bupivacaine in a tibial plateau leveling osteotomy model

“…The reported concentration of free bupivacaine in liposomal bupivacaine suspensions is 1.064 mg/mL, 22 which is less than the free bupivacaine concentrations in any of our samples, including the control (1.90 mg/mL). Carlson et al 22 found an average of 1.2 mg/mL when they assayed free bupivacaine concentration using the same method we used. However, their samples were taken from the liposomal bupivacaine vial and immediately processed on site.…”

“…All samples were stored, prepared, and analyzed as described by Carlson and colleagues 22 . Liposomal bupivacaine samples were centrifuged at 3500 g for 30 minutes at 4°C.…”

“…All samples were stored, prepared, and analyzed as described by Carlson and colleagues. 22 Liposomal bupivacaine samples were centrifuged at 3500 g for 30 minutes at 4 C. Two hundred fifty microliters of supernatant was collected and stored at −80 C until analysis. Unencapsulated bupivacaine concentrations were determined by using high-performance liquid chromatography (HPLC; 1 101 260 Infinity HPLC system with a multiwavelength detector; Agilent Technologies, Wilmington, Delaware).…”

Effect of bupivacaine concentration and formulation on canine chondrocyte viability in vitro

“…This resulted in a decrease in colony survival similar to that in SFB. The short-term lack of toxicity may be related to the low concentration of free bupivacaine achieved by using LEB (approximately 1.2 mg/mL 23 ). In an in vitro study, Shaw et al 16 treated bovine chondrocytes with LEB for 1 hour and found no difference compared with saline and a significant difference from 5 mg/mL SFB when evaluated by using flow cytometry.…”

“…This was to better emulate clinical use of a 10‐fold dilution of stock bupivacaine and because no difference was seen between 0.4 and 0.6 mg/mL SFB according to MTT assay (Table 1). Undiluted LEB is expected to result in a free bupivacaine concentration of approximately 1.2 mg/mL, 23 and the product label allows for dilution of up to 50% by volume when saline is used 24 . All dilutions of bupivacaine were performed with 0.9% saline.…”