Stability testing of piperacilline/tazobactam in elastomeric infusion pumps

Abstract

Background & objectives Currently, the University Hospital Basel is running an outpatient parenteral antibiotic therapy (OPAT) program which uses elastomeric infusion pumps for continuous application of certain antibiotics. To prepare piperacilline (PIP)/tazobactam (TAZ) pumps in advance, the original brand is used (Tazobac®), as recommended by several guidelines. This study aims to investigate whether a generic brand shows sufficient stability under the following conditions in the OPAT program: manufacturing pumps in advance, storing them refrigerated and administrating them at elevated temperatures (37 °C), when pumps are placed close to the patient's body. The stability of two different pump compositions was evaluated to examine the influence of an additional buffer (as contained in Tazobac®) on the chemical stability of the PIP/TAZ solution. Methods Preparation and sampling of solutions in pumps: a total of six pumps were prepared, each containing 12/1.5 g PIP/TAZ in 0.9% sodium chloride. Three of the six pumps were buffered using 17 mL of 4% sodium citrate. All pumps were filled up to 240 mL using 0.9% sodium chloride. A sample was drawn immediately thereafter. The pumps were kept in the refrigerator for seven days and then kept outside for one hour before a second sample was taken. After keeping the pumps for additional 12 hours at 37 °C, a third sample was taken and then samples were drawn every three hours for up to 12 hours, while keeping the pumps at 37 °C. Samples were frozen and analyzed within seven weeks. Assay: a validated HPLC method was used to determine drug concentration. The method employed a reversed phase C18 column (ACE RP 18.3 μm 4.0 × 75 mm, Fa LCC), with retention time of PIP at 7.3 minutes and TAZ at 2.3 minutes and a detection wavelength of 230 nm. Mobile phase consisted of a phosphate buffer adjusted to pH 5.5 and methanol. The initial concentration was defined as 100% and subsequent concentrations were calculated as percentages of the initial concentration. Acceptance criteria for stability were defined as 90–110% of initial concentration. Results The lowest concentration of PIP for the generic pumps was 89% and of TAZ 92%. The lowest concentration for PIP and TAZ for the generic pumps with buffer was 94% and 95% respectively. Discussion & conclusions The buffer shows a positive effect on stability of PIP and TAZ in elastomeric pumps prepared with the generic brand. The stability was proven under simulated OPAT conditions. The savings of switching from Tazobac® to the generic brand are estimated to outweigh the expenses of buffering the pumps.