Physicochemical stability of nanoparticle albumin-bound paclitaxel (Pazenir^®) infusion dispersion in original glass vials and EVA infusion bags

Background and importance
Pazenir^® powder for dispersion for infusion is authorised in the EU since 2019 for treatment of metastatic breast, pancreas, and lung cancer. Pazenir® contains lyophilised nanoparticle albumin-bound paclitaxel (nab-paclitaxel) to be reconstituted with 0.9% sodium chloride and transferred into an infusion bag prior to administration. According to the SmPC, the reconstituted dispersion is physicochemically stable in the vial and infusion bag for 24 hours at 2-8 °C followed by 4 hours at 15-25 °C. To our knowledge, prolonged stability data for Pazenir® infusion dispersion are not published yet.

Aim and objectives
Investigation of physicochemical stability of nab-paclitaxel (Pazenir^®) reconstituted dispersion for infusion in the original glass vial and ready-to-administer (RTA) infusion dispersion in EVA bags with orthogonal methods.

Materials and methods
Pazenir^® test solutions were prepared in triplicate and either stored in the original glass vials or transferred into empty 150 mL EVA bags. Test solutions were stored at 2-8 °C or 25 °C for 28 days. Directly after reconstitution and on day 1, 3, 5, 7, 14, 21, and 28 samples were withdrawn and paclitaxel concentrations assayed by a stability-indicating HPLC method. In parallel, pH and osmolality were measured. Another series of test solutions was prepared, stored in the same way, and samples daily withdrawn up to day 14. Albumin oligomers, polymers or aggregates were determined by size-exclusion-chromatography (SEC). Integrity of the nanoparticles was determined by dynamic light scattering (DLS). At each sampling time-point dispersion were inspected visually for particles and color changes.

Results
Paclitaxel concentrations remained above 95% of the initial concentrations for 7 and 14 days in vials and EVA bags stored at 2-8 °C, respectively. All test dispersions met the specifications regarding the oligomeric status of albumin during the 14-day period. The nanoparticles remained intact for 11 days in Pazenir® vials and in EVA bags stored refrigerated and for 6 days in EVA bags stored at 25 °C. Non-dispersible particles were observed in test dispersions after 4 days (EVA bags stored at 25 °C), 8 days (EVA bags stored at 2-8 °C), and 10 days (vials stored at 2-8 °C). Values of pH and osmolality met the specifications during the whole investigation period.

Discussion and conclusion
Physicochemical stability of nab-Paclitaxel is temperature-dependent. Refrigerated storage is recommended. Aggregate formation was detected by the different analytical methods at different time points. Based on the results of the orthogonal methods used, nab-paclitaxel (Pazenir^®) revealed to be physicochemically stable for 7 days reconstituted in the original vials and stored at 2-8 °C. RTA infusion dispersions in EVA bags are physicochemically stable for 7 days when stored at 2-8 °C or 4 days when stored at 25 °C.