From Bench to Bulk: Exploring In-Line Homogenization for Scale-Up and Continuous Production of Vesicular Systems

From Bench to Bulk: Exploring In-Line Homogenization for Scale-Up and Continuous Production of Vesicular Systems | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article From Bench to Bulk: Exploring In-Line Homogenization for Scale-Up and Continuous Production of Vesicular Systems Kshitija M. Phatak, Ankita N. Yawalkar, Pradeep R Vavia This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7651329/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 30 Jan, 2026 Read the published version in Drug Delivery and Translational Research → Version 1 posted 5 You are reading this latest preprint version Abstract Nanovesicular systems hold a significant promise for drug delivery, yet their clinical translation is hindered by challenges in scalability and reproducibility. This study introduces in-line homogenization as a continuous, organic solvent-free approach for scalable fabrication of bilayered unilamellar vesicles, NioTherms (Niosome-like) and ThermoSomes (Liposome-like), loaded with model hydrophobic (Posaconazole, PCZ) and hydrophilic (Dexamethasone Sodium Phosphate, DEX) drugs. Using a heat-mixing method as the baseline, formulations were scaled from 10 mL (1x) to 1 L (100x) via a rotor-stator-based in-line homogenizer. Process parameters including pump speed, homogenizer speed, cycle number, phase ratio and output rate were optimized. The resulting vesicles exhibited uniform particle size and entrapment efficiencies comparable to the lab-scale batches. The formation of vesicles, morphology, internal structure, and integrity of the formed particles was confirmed by TEM and SANS analysis. The system enabled rapid batch processing (< 5 minutes for 1 L) with substantial product yields up to 80%. The process demonstrated excellent reproducibility and eliminated the need for post-processing. This study establishes in-line homogenization as a robust, scalable platform for faster production of nanovesicular drug delivery systems, effectively bridging the gap between bench-scale development and continuous manufacturing. continuous production scale-up in-line homogenizer pilot scale vesicular system nanoformulations Full Text Supplementary Files Scaleupinlinehomogenizervideo.mp4 Cite Share Download PDF Status: Published Journal Publication published 30 Jan, 2026 Read the published version in Drug Delivery and Translational Research → Version 1 posted Editorial decision: Major Revisions Needed 10 Nov, 2025 Reviewers agreed at journal 13 Oct, 2025 Reviewers invited by journal 13 Oct, 2025 Editor assigned by journal 22 Sep, 2025 First submitted to journal 19 Sep, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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