Preparation of curcumin submicron particles by supercritical antisolvent method with external adjustable annular gap nozzle

Abstract The supercritical antisolvent (SAS) method can effectively improve the bioavailability of poorly water-soluble drugs. However, the current supercritical equipment and processes were not fully developed, making industrialization difficult to achieve. Therefore, an externally adjustable annul...

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Main Authors: Yechen Wang, Zirui Li, Sun Fayu, Fei Li, Weiqiang Wang
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-87787-x
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author Yechen Wang
Zirui Li
Sun Fayu
Fei Li
Weiqiang Wang
author_facet Yechen Wang
Zirui Li
Sun Fayu
Fei Li
Weiqiang Wang
author_sort Yechen Wang
collection DOAJ
description Abstract The supercritical antisolvent (SAS) method can effectively improve the bioavailability of poorly water-soluble drugs. However, the current supercritical equipment and processes were not fully developed, making industrialization difficult to achieve. Therefore, an externally adjustable annular gap nozzle and its supporting equipment were designed. Curcumin was used as a model drug, ethanol as the solvent, and supercritical carbon dioxide (SC-CO2) as the antisolvent. Building on single-factor experiments, a Box-Behnken Design-Response Surface Methodology (BBD-RSM) was employed to systematically investigate the effects of four process parameters—crystallizer pressure (12–16 MPa), crystallizer temperature (313–323 K), solution concentration (1–2 mg/mL), and CO2/solution flow rate ratio (133–173 g/g)—on the morphology and particle size of curcumin particles. Using scanning electron microscopy (SEM) and dynamic light scattering (DLS) analyses, morphologies and mean diameter ranges were examined. To look into how the SAS process affects TML’s chemical and physical characteristics, X-ray diffraction analysis (XRD) and Fourier-transform infrared spectroscopy (FT-IR) were further performed. Experimental results show that, flow ratio of CO2/solution had the greatest effect of particle size, followed by crystallizer temperature and solution concentration, while crystallizer pressure had the least influence. The optimum process conditions are operational conditions were set with a crystallizer pressure of 15 MPa, crystallizer temperature of 320 K, solution concentration of 1.2 mg/mL, and flow ratio of CO2/solution of 134 g/g, resulting in curcumin submicron particles with an average particle size of 808 nm being obtained. This study demonstrated the feasibility of an externally adjustable annular gap nozzle and its associated equipment in the SAS process, showcasing significant potential for reducing particles size and enhancing the bioavailability of poorly water-soluble drugs.
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spelling doaj-art-12f183f0cbd34db9a3b81ba1ff038abf2025-02-02T12:19:07ZengNature PortfolioScientific Reports2045-23222025-01-0115111710.1038/s41598-025-87787-xPreparation of curcumin submicron particles by supercritical antisolvent method with external adjustable annular gap nozzleYechen Wang0Zirui Li1Sun Fayu2Fei Li3Weiqiang Wang4Key Laboratory of High-efficiency and Clean Mechanical Manufacture (Ministry of Education), National Demonstration Center for Experimental Mechanical Engineering Education (Shandong University), School of Mechanical Engineering, Shandong UniversityKey Laboratory of High-efficiency and Clean Mechanical Manufacture (Ministry of Education), National Demonstration Center for Experimental Mechanical Engineering Education (Shandong University), School of Mechanical Engineering, Shandong UniversityKey Laboratory of High-efficiency and Clean Mechanical Manufacture (Ministry of Education), National Demonstration Center for Experimental Mechanical Engineering Education (Shandong University), School of Mechanical Engineering, Shandong UniversityKey Laboratory of High-efficiency and Clean Mechanical Manufacture (Ministry of Education), National Demonstration Center for Experimental Mechanical Engineering Education (Shandong University), School of Mechanical Engineering, Shandong UniversityKey Laboratory of High-efficiency and Clean Mechanical Manufacture (Ministry of Education), National Demonstration Center for Experimental Mechanical Engineering Education (Shandong University), School of Mechanical Engineering, Shandong UniversityAbstract The supercritical antisolvent (SAS) method can effectively improve the bioavailability of poorly water-soluble drugs. However, the current supercritical equipment and processes were not fully developed, making industrialization difficult to achieve. Therefore, an externally adjustable annular gap nozzle and its supporting equipment were designed. Curcumin was used as a model drug, ethanol as the solvent, and supercritical carbon dioxide (SC-CO2) as the antisolvent. Building on single-factor experiments, a Box-Behnken Design-Response Surface Methodology (BBD-RSM) was employed to systematically investigate the effects of four process parameters—crystallizer pressure (12–16 MPa), crystallizer temperature (313–323 K), solution concentration (1–2 mg/mL), and CO2/solution flow rate ratio (133–173 g/g)—on the morphology and particle size of curcumin particles. Using scanning electron microscopy (SEM) and dynamic light scattering (DLS) analyses, morphologies and mean diameter ranges were examined. To look into how the SAS process affects TML’s chemical and physical characteristics, X-ray diffraction analysis (XRD) and Fourier-transform infrared spectroscopy (FT-IR) were further performed. Experimental results show that, flow ratio of CO2/solution had the greatest effect of particle size, followed by crystallizer temperature and solution concentration, while crystallizer pressure had the least influence. The optimum process conditions are operational conditions were set with a crystallizer pressure of 15 MPa, crystallizer temperature of 320 K, solution concentration of 1.2 mg/mL, and flow ratio of CO2/solution of 134 g/g, resulting in curcumin submicron particles with an average particle size of 808 nm being obtained. This study demonstrated the feasibility of an externally adjustable annular gap nozzle and its associated equipment in the SAS process, showcasing significant potential for reducing particles size and enhancing the bioavailability of poorly water-soluble drugs.https://doi.org/10.1038/s41598-025-87787-xSupercritical antisolventAdjustable annular gap nozzleCurcuminSubmicron particlesBox–Behnken designs
spellingShingle Yechen Wang
Zirui Li
Sun Fayu
Fei Li
Weiqiang Wang
Preparation of curcumin submicron particles by supercritical antisolvent method with external adjustable annular gap nozzle
Scientific Reports
Supercritical antisolvent
Adjustable annular gap nozzle
Curcumin
Submicron particles
Box–Behnken designs
title Preparation of curcumin submicron particles by supercritical antisolvent method with external adjustable annular gap nozzle
title_full Preparation of curcumin submicron particles by supercritical antisolvent method with external adjustable annular gap nozzle
title_fullStr Preparation of curcumin submicron particles by supercritical antisolvent method with external adjustable annular gap nozzle
title_full_unstemmed Preparation of curcumin submicron particles by supercritical antisolvent method with external adjustable annular gap nozzle
title_short Preparation of curcumin submicron particles by supercritical antisolvent method with external adjustable annular gap nozzle
title_sort preparation of curcumin submicron particles by supercritical antisolvent method with external adjustable annular gap nozzle
topic Supercritical antisolvent
Adjustable annular gap nozzle
Curcumin
Submicron particles
Box–Behnken designs
url https://doi.org/10.1038/s41598-025-87787-x
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AT sunfayu preparationofcurcuminsubmicronparticlesbysupercriticalantisolventmethodwithexternaladjustableannulargapnozzle
AT feili preparationofcurcuminsubmicronparticlesbysupercriticalantisolventmethodwithexternaladjustableannulargapnozzle
AT weiqiangwang preparationofcurcuminsubmicronparticlesbysupercriticalantisolventmethodwithexternaladjustableannulargapnozzle