Comparative Analysis of Nebulizers in Clinical use for Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC)

Abstract

AbstractObjectiveTechnical ex-vivo comparison of commercial nebulizer nozzles used for Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC).MethodsThe performance of four different commercial nebulizer nozzles (Nebulizer; HurriChem™; MCR-4 TOPOL®; QuattroJet) was analysed by comparing: i) technical design and principle of operation, ii) operational pressure as function of the liquid flow rate, iii) droplet size distribution via laser diffraction spectrometry, iv) spray cone angle, spray cone form, and horizontal drug deposition through image-metric analyses, and v) chemical resistance via exposing to a cytostatic solution and metallurgic composition by means of spark optical emission spectral analysis.ResultsThe Nebulizer exhibits a nearly identical technical design, implying a comparable performance (e.g., mass median droplet size of 29 μm) as the original PIPAC nozzles (MIP/ CapnoPen). The other three nozzles demonstrate varying degrees of performance deviation from the original PIPAC nozzles. The HurriChem™ shares a similar design and principle of operation as the Nebulizer, but produces a finer aerosol with a particle size of 22 μm. The operating principles of MCR-4 TOPOL®and QuattroJet significantly differ from that of the original PIPAC nozzle technology. The MCR-4 TOPOL®nebulizer has a hollow spray cone that leads to the production of significantly larger aerosol droplets (50 μm) compared to the original PIPAC nozzles. The QuattroJet generates an aerosol droplet (22 μm) similar in size to the HurriChem™ and exhibits improved spatial drug distribution.ConclusionWhile the introduction of new PIPAC nozzles is a welcome development, differences in performance and efficacy were noted. Therefore, it is recommended that PIPAC nozzles that deviate from the current standard undergo bioequivalence testing and be implemented in accordance with the IDEAL-D framework prior to routine clinical use.