The first formulation tailored for intraperitoneal delivery as a pressurised aerosol (PIPAC): doxorubicin-cisplatin as a fixed, ready-to-use drug combination

Pressurised Intraperitoneal Aerosol Chemotherapy (PIPAC) is a novel drug delivery system for treating peritoneal metastasis. No PIPAC-specific formulation is available, stability data under PIPAC conditions are lacking, and the drugs are used off-label. 85% PIPAC are performed using Doxorubicin (DOX) and Cisplatin (CIS). Formulation development adhered to Investigational Medicinal Product Dossier (IMPD) requirements, covering composition, manufacturing process and controls, characterisation of actives and excipients, and in-use and long-term stability, as well as preclinical validation, including sprayability and dose equivalence in peritoneal tissue. The drug composition meets defined pharmaceutical specifications, yielding a stable, ready-to-use aqueous solution containing 0.131 mg/mL DOX and 0.656 mg/mL CIS in 0.9% sodium chloride, buffered to pH 4.4-4.5. Manufacturing followed a scalable process with controlled pH, osmolality, and purity, and packaging ensured light protection. Characterisation confirmed stability, appropriate viscosity, and physicochemical integrity. Sprayability testing with the CapnoPen® device demonstrated consistent aerosolisation and no drug-device incompatibility. A 200 mL volume provided optimal tissue uptake and lowest aerosol sedimentation, outperforming 100 mL and matching reference drugs. Tissue bioavailability of DOX and CIS was comparable to that of separate drug administration. Usability studies showed simplified handling, reduced equipment needs and minimised exposure risks. The diluted solution was stable for up to 30 h at room temperature, while long-term stability at 5 °C (undiluted) preserved DOX for 9 months and CIS for 60 months. We developed a sprayable DOX-CIS formulation specifically tailored for PIPAC therapy. Overall, the DOX-CIS composition met the predefined quality, performance, and stability criteria for use in PIPAC.