{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:46:12Z","timestamp":1791927972163,"version":"4.3.4"},"reference-count":23,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Capnomed GmbH, Tuebingen, Germany"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Drug Deliv. and Transl. Res."],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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\u2009mg\/mL DOX and 0.656\u2009mg\/mL CIS in 0.9% sodium chloride, buffered to pH 4.4\u20134.5. 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\u00ae device demonstrated consistent aerosolisation and no drug-device incompatibility. A 200\u2009mL volume provided optimal tissue uptake and lowest aerosol sedimentation, outperforming 100\u2009mL 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\u2009h at room temperature, while long-term stability at 5\u2009\u00b0C (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.<\/jats:p>","DOI":"10.1007\/s13346-026-02229-z","type":"journal-article","created":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:00:38Z","timestamp":1791925238000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The first formulation tailored for intraperitoneal delivery as a pressurised aerosol (PIPAC): doxorubicin-cisplatin as a fixed, ready-to-use drug combination"],"prefix":"10.1007","author":[{"given":"Yaroslaw","family":"Sautkin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranjita","family":"Shegokar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janek","family":"Kibat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona","family":"Kibat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juergen","family":"Weinreich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Schoenfelder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc Andr\u00e9","family":"Reymond","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,13]]},"reference":[{"key":"2229_CR1","doi-asserted-by":"publisher","first-page":"20180102","DOI":"10.1515\/pp-2018-0102","volume":"3","author":"J Franko","year":"2018","unstructured":"Franko J. 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YS, JW and MAR were employees of the University Hospital Tuebingen, Germany, during the research period. MK was a student at the University of Tuebingen, Germany. JK and RS were employees of Capnomed GmbH. MAR has a shareholder interest in Capnomed GmbH.","order":1,"name":"Ethics","label":"Disclosure","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This research was funded by Capnomed GmbH, Tuebingen, Germany, and performed at the National Centre for Pleura and Peritoneum\u2019s research lab at the University Hospital Tuebingen, Germany. DOX-CIS composition is protected by the patents US20210267887A1 | EP3586823A1 | EP3606508A1 |EP3606508B1 | WO2020002258A1, and the Trademarks EUIPO 1483283, and USPTO 79265547. YS, JW and MAR were employees of the University Hospital Tuebingen, Germany, during the research period. MK was a student at the University of Tuebingen, Germany. JK and RS were employees of Capnomed GmbH. MAR has a shareholder interest in Capnomed GmbH.","order":2,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}]}}