---
title: "Pilot-scale transfer and optimization of a supercritical CO2 PGSS method for producing drug-loaded"
id: "pubmed-42551720"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42551720"
content_type: "clinical_feed_article"
specialty: "Pharmacology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42551720/"
doi: "10.1016/j.ijpharm.2026.127281"
published_at: "2026-09-05T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Pilot-scale transfer and optimization of a supercritical CO2 PGSS method for producing drug-loaded
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42551720
- **Specialty:** [Pharmacology](https://medichelpline.com/clinical-feed/pharmacology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42551720/)
- **DOI:** [10.1016/j.ijpharm.2026.127281](https://doi.org/10.1016%2Fj.ijpharm.2026.127281)
- **Published At:** 2026-09-05T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- The study reports successful transfer of a supercritical CO2-based **PGSS** (Particles from Gas-Saturated Solutions) liposome production process from laboratory to pilot scale, expanding reactor volume from 50 mL to 500 mL. - A **Quality by Design** approach with a design of experiments on a simplified soy phosphatidylcholine formulation was used to identify and optimize key process parameters for scale-up. - Optimized parameters were validated across multiple drug-encapsulating liposome formulations, demonstrating **process robustness** and transferability. - At pilot scale, the process reproducibly produced **liposomes** with mean diameters below 200 nm and polydispersity indices near 0.30. - The PGSS process was applied successfully to drug-loaded formulations, achieving **high encapsulation efficiencies** while preserving suitable physicochemical properties. - Cryo-TEM imaging confirmed consistent formation of vesicular structures in the produced formulations. - Lipid chemical stability was maintained during the process, with only minimal hydrolysis and no significant increase in oxidation, including for unsaturated lipids. - The method is described as **solvent-free** and single-step, highlighting its potential industrial relevance for scalable liposome manufacturing while maintaining critical quality attributes and formulation stability. - The paper concludes that the PGSS supercritical CO2 approach is robust, scalable, and relevant as an alternative liposome production technology for drug encapsulation. - Details on exact optimized parameter values, specific drug compounds used, and quantitative encapsulation efficiency values were not reported in the abstract and require consultation of the full text for numbers and procedural specifics.
## Clinical Analysis & Structured Key Points
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Epub 2026 Aug 4. # Pilot scale transfer and optimization of an innovative supercritical CO2 PGSS method for the production of drug-encapsulating liposomes [Tuan Nghia Dinh](https://pubmed.ncbi.nlm.nih.gov/?term=Dinh+TN&cauthor_id=42551720)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42551720/#full-view-affiliation-1 "Laboratory of Pharmaceutical Technology and Biopharmacy, Center for Interdisciplinary Research on Medicines, University of Liège, 4000 Liège, Belgium."), [Chloé Gauthy](https://pubmed.ncbi.nlm.nih.gov/?term=Gauthy+C&cauthor_id=42551720)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42551720/#full-view-affiliation-1 "Laboratory of Pharmaceutical Technology and Biopharmacy, Center for Interdisciplinary Research on Medicines, University of Liège, 4000 Liège, Belgium."), [Hugo Magdalena Segura](https://pubmed.ncbi.nlm.nih.gov/?term=Magdalena+Segura+H&cauthor_id=42551720)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42551720/#full-view-affiliation-1 "Laboratory of Pharmaceutical Technology and Biopharmacy, Center for Interdisciplinary Research on Medicines, University of Liège, 4000 Liège, Belgium."), [Pierre-Yves Sacré](https://pubmed.ncbi.nlm.nih.gov/?term=Sacr%C3%A9+PY&cauthor_id=42551720)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42551720/#full-view-affiliation-2 "Research Support Unit in Chemometrics, Center for Interdisciplinary Research on Medicines, University of Liège, 4000 Liège, Belgium."), [Erika Hendrickx](https://pubmed.ncbi.nlm.nih.gov/?term=Hendrickx+E&cauthor_id=42551720)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42551720/#full-view-affiliation-3 "Center for Microscopy and Molecular Imaging \(CMMI\), Université Libre de Bruxelles, 6041 Gosselies, Belgium."), [Louise Conrard](https://pubmed.ncbi.nlm.nih.gov/?term=Conrard+L&cauthor_id=42551720)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42551720/#full-view-affiliation-3 "Center for Microscopy and Molecular Imaging \(CMMI\), Université Libre de Bruxelles, 6041 Gosselies, Belgium."), [Brigitte Evrard](https://pubmed.ncbi.nlm.nih.gov/?term=Evrard+B&cauthor_id=42551720)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42551720/#full-view-affiliation-1 "Laboratory of Pharmaceutical Technology and Biopharmacy, Center for Interdisciplinary Research on Medicines, University of Liège, 4000 Liège, Belgium."), [Brigitte Malgrange](https://pubmed.ncbi.nlm.nih.gov/?term=Malgrange+B&cauthor_id=42551720)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42551720/#full-view-affiliation-4 "Developmental Neurobiology Laboratory, GIGA-Stem Cells, University of Liège, 4000 Liège, Belgium."), [Géraldine Piel](https://pubmed.ncbi.nlm.nih.gov/?term=Piel+G&cauthor_id=42551720)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42551720/#full-view-affiliation-5 "Laboratory of Pharmaceutical Technology and Biopharmacy, Center for Interdisciplinary Research on Medicines, University of Liège, 4000 Liège, Belgium. Electronic address: geraldine.piel@uliege.be."), [Noémie Penoy](https://pubmed.ncbi.nlm.nih.gov/?term=Penoy+N&cauthor_id=42551720)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42551720/#full-view-affiliation-1 "Laboratory of Pharmaceutical Technology and Biopharmacy, Center for Interdisciplinary Research on Medicines, University of Liège, 4000 Liège, Belgium.") Affiliations Expand ### Affiliations * 1 Laboratory of Pharmaceutical Technology and Biopharmacy, Center for Interdisciplinary Research on Medicines, University of Liège, 4000 Liège, Belgium. * 2 Research Support Unit in Chemometrics, Center for Interdisciplinary Research on Medicines, University of Liège, 4000 Liège, Belgium. * 3 Center for Microscopy and Molecular Imaging (CMMI), Université Libre de Bruxelles, 6041 Gosselies, Belgium. * 4 Developmental Neurobiology Laboratory, GIGA-Stem Cells, University of Liège, 4000 Liège, Belgium. * 5 Laboratory of Pharmaceutical Technology and Biopharmacy, Center for Interdisciplinary Research on Medicines, University of Liège, 4000 Liège, Belgium. Electronic address: geraldine.piel@uliege.be. * PMID: **42551720** * DOI: [ 10.1016/j.ijpharm.2026.127281 ](https://doi.org/10.1016/j.ijpharm.2026.127281) Item in Clipboard # Pilot scale transfer and optimization of an innovative supercritical CO2 PGSS method for the production of drug-encapsulating liposomes Tuan Nghia Dinh et al. Int J Pharm. 2026. Show details Display options Display options Format Abstract PubMed PMID Int J Pharm Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Int+J+Pharm%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Int+J+Pharm%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42551720/) . 2026 Sep 5:702:127281. doi: 10.1016/j.ijpharm.2026.127281. Epub 2026 Aug 4. ### Authors [Tuan Nghia Dinh](https://pubmed.ncbi.nlm.nih.gov/?term=Dinh+TN&cauthor_id=42551720)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42551720/#short-view-affiliation-1 "Laboratory of Pharmaceutical Technology and Biopharmacy, Center for Interdisciplinary Research on Medicines, University of Liège, 4000 Liège, Belgium."), [Chloé Gauthy](https://pubmed.ncbi.nlm.nih.gov/?term=Gauthy+C&cauthor_id=42551720)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42551720/#short-view-affiliation-1 "Laboratory of Pharmaceutical Technology and Biopharmacy, Center for Interdisciplinary Research on Medicines, University of Liège, 4000 Liège, Belgium."), [Hugo Magdalena Segura](https://pubmed.ncbi.nlm.nih.gov/?term=Magdalena+Segura+H&cauthor_id=42551720)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42551720/#short-view-affiliation-1 "Laboratory of Pharmaceutical Technology and Biopharmacy, Center for Interdisciplinary Research on Medicines, University of Liège, 4000 Liège, Belgium."), [Pierre-Yves Sacré](https://pubmed.ncbi.nlm.nih.gov/?term=Sacr%C3%A9+PY&cauthor_id=42551720)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42551720/#short-view-affiliation-2 "Research Support Unit in Chemometrics, Center for Interdisciplinary Research on Medicines, University of Liège, 4000 Liège, Belgium."), [Erika Hendrickx](https://pubmed.ncbi.nlm.nih.gov/?term=Hendrickx+E&cauthor_id=42551720)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42551720/#short-view-affiliation-3 "Center for Microscopy and Molecular Imaging \(CMMI\), Université Libre de Bruxelles, 6041 Gosselies, Belgium."), [Louise Conrard](https://pubmed.ncbi.nlm.nih.gov/?term=Conrard+L&cauthor_id=42551720)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42551720/#short-view-affiliation-3 "Center for Microscopy and Molecular Imaging \(CMMI\), Université Libre de Bruxelles, 6041 Gosselies, Belgium."), [Brigitte Evrard](https://pubmed.ncbi.nlm.nih.gov/?term=Evrard+B&cauthor_id=42551720)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42551720/#short-view-affiliation-1 "Laboratory of Pharmaceutical Technology and Biopharmacy, Center for Interdisciplinary Research on Medicines, University of Liège, 4000 Liège, Belgium."), [Brigitte Malgrange](https://pubmed.ncbi.nlm.nih.gov/?term=Malgrange+B&cauthor_id=42551720)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42551720/#short-view-affiliation-4 "Developmental Neurobiology Laboratory, GIGA-Stem Cells, University of Liège, 4000 Liège, Belgium."), [Géraldine Piel](https://pubmed.ncbi.nlm.nih.gov/?term=Piel+G&cauthor_id=42551720)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42551720/#short-view-affiliation-5 "Laboratory of Pharmaceutical Technology and Biopharmacy, Center for Interdisciplinary Research on Medicines, University of Liège, 4000 Liège, Belgium. Electronic address: geraldine.piel@uliege.be."), [Noémie Penoy](https://pubmed.ncbi.nlm.nih.gov/?term=Penoy+N&cauthor_id=42551720)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42551720/#short-view-affiliation-1 "Laboratory of Pharmaceutical Technology and Biopharmacy, Center for Interdisciplinary Research on Medicines, University of Liège, 4000 Liège, Belgium.") ### Affiliations * 1 Laboratory of Pharmaceutical Technology and Biopharmacy, Center for Interdisciplinary Research on Medicines, University of Liège, 4000 Liège, Belgium. * 2 Research Support Unit in Chemometrics, Center for Interdisciplinary Research on Medicines, University of Liège, 4000 Liège, Belgium. * 3 Center for Microscopy and Molecular Imaging (CMMI), Université Libre de Bruxelles, 6041 Gosselies, Belgium. * 4 Developmental Neurobiology Laboratory, GIGA-Stem Cells, University of Liège, 4000 Liège, Belgium. * 5 Laboratory of Pharmaceutical Technology and Biopharmacy, Center for Interdisciplinary Research on Medicines, University of Liège, 4000 Liège, Belgium. Electronic address: geraldine.piel@uliege.be. * PMID: **42551720** * DOI: [ 10.1016/j.ijpharm.2026.127281 ](https://doi.org/10.1016/j.ijpharm.2026.127281) Item in Clipboard Full text links Cite Display options Display options Format Abstract PubMed PMID ## Abstract The industrial translation of liposome production processes remains challenging, particularly in achieving scalability while maintaining critical quality attributes and formulation stability. In this study, a supercritical CO2-based PGSS process was successfully transferred from the laboratory to the pilot scale (50 to 500 mL reactor). Using a Quality by Design approach and a design of experiments on a simplified soy phosphatidylcholine formulation, we identified optimal production process parameters. These parameters were then validated and transferred to other drug-encapsulating liposome formulations, demonstrating process robustness. Under these conditions, liposomes measuring less than 200 nm and polydispersity indices close to 0.30 were reproducibly obtained at pilot scale. The process was successfully applied to drug-loaded formulations, achieving high encapsulation efficiencies while maintaining suitable physicochemical properties. Cryo-TEM confirmed the formation of consistent vesicular structures. Importantly, lipid chemical stability was preserved, with minimal hydrolysis and no significant increase in oxidation, even for unsaturated lipids. Overall, this study demonstrates the robustness, scalability, and relevance of the PGSS process as a solvent-free, single-step technology for liposome production. **Keywords:** Drug encapsulation; Liposome production method; Liposomes; Pilot scale; Supercritical carbon dioxide. Copyright © 2026 Elsevier B.V. All rights reserved. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. ## Similar articles * [ A supercritical fluid technology for liposome production and comparison with the film hydration method. ](https://pubmed.ncbi.nlm.nih.gov/33212171/) Penoy N, Grignard B, Evrard B, Piel G.Penoy N, et al.Int J Pharm. 2021 Jan 5;592:120093. doi: 10.1016/j.ijpharm.2020.120093. Epub 2020 Nov 16.Int J Pharm. 2021.PMID: 33212171 * [ An innovative one step green supercritical CO2 process for the production of liposomes co-encapsulating both a hydrophobic and a hydrophilic compound for pulmonary administration. ](https://pubmed.ncbi.nlm.nih.gov/36150416/) Penoy N, Delma KL, Tonakpon HA, Grignard B, Evrard B, Piel G.Penoy N, et al.Int J Pharm. 2022 Nov 5;627:122212. doi: 10.1016/j.ijpharm.2022.122212. Epub 2022 Sep 21.Int J Pharm. 2022.PMID: 36150416 * [ Scalable microfluidic method for tunable liposomal production by a design of experiment approach. ](https://pubmed.ncbi.nlm.nih.gov/39004291/) Buttitta G, Bonacorsi S, Barbarito C, Moliterno M, Pompei S, Saito G, Oddone I, Verdone G, Secci D, Raimondi S.Buttitta G, et al.Int J Pharm. 2024 Sep 5;662:124460. doi: 10.1016/j.ijpharm.2024.124460. Epub 2024 Jul 14.Int J Pharm. 2024.PMID: 39004291 * [ Nanoparticles in the pharmaceutical industry and the use of supercritical fluid technologies for nanoparticle production. ](https://pubmed.ncbi.nlm.nih.gov/22283656/) Sheth P, Sandhu H, Singhal D, Malick W, Shah N, Kislalioglu MS.Sheth P, et al.Curr Drug Deliv. 2012 May;9(3):269-84. doi: 10.2174/156720112800389052.Curr Drug Deliv. 2012.PMID: 22283656Review. * [ Current data on ATP-containing liposomes and potential prospects to enhance cellular energy status for hepatic applications. ](https://pubmed.ncbi.nlm.nih.gov/18540841/) Korb V, Tep K, Escriou V, Richard C, Scherman D, Cynober L, Chaumeil J, Dumortier G.Korb V, et al.Crit Rev Ther Drug Carrier Syst. 2008;25(4):305-45. doi: 10.1615/critrevtherdrugcarriersyst.v25.i4.10.Crit Rev Ther Drug Carrier Syst. 2008.PMID: 18540841Review. [ See all similar articles ](https://pubmed.ncbi.nlm.nih.gov/?linkname=pubmed_pubmed&from_uid=42551720) ## MeSH terms * Carbon Dioxide* / chemistry Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Carbon+Dioxide%2Fchemistry%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Carbon+Dioxide) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42551720/) * Chemistry, Pharmaceutical / methods Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Chemistry%2C+Pharmaceutical%2Fmethods%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Chemistry%2C+Pharmaceutical) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42551720/) * Drug Compounding* / methods Actions * [ Sear
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