Wang Yechen, Li Zirui, Fayu Sun, Li Fei, Wang Weiqiang
Key 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 University, Jinan, 250061, People's Republic of China.
University of Health and Rehabilitation Sciences, Qingdao, 266071, People's Republic of China.
Sci Rep. 2025 Jan 26;15(1):3312. doi: 10.1038/s41598-025-87787-x.
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-CO) 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 CO/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 CO/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 CO/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.
超临界抗溶剂（SAS）法可有效提高难溶性药物的生物利用度。然而，目前的超临界设备和工艺尚未完全成熟，难以实现工业化。因此，设计了一种外部可调的环形间隙喷嘴及其配套设备。以姜黄素为模型药物，乙醇为溶剂，超临界二氧化碳（SC-CO）为抗溶剂。在单因素实验的基础上，采用Box-Behnken设计-响应面法（BBD-RSM）系统研究了四个工艺参数——结晶器压力（12-16MPa）、结晶器温度（313-323K）、溶液浓度（1-2mg/mL）和CO/溶液流速比（133-173g/g）——对姜黄素颗粒形态和粒径的影响。通过扫描电子显微镜（SEM）和动态光散射（DLS）分析，检测了颗粒形态和平均直径范围。为了研究SAS工艺如何影响姜黄素的化学和物理特性，进一步进行了X射线衍射分析（XRD）和傅里叶变换红外光谱（FT-IR）分析。实验结果表明，CO/溶液流速比对粒径的影响最大，其次是结晶器温度和溶液浓度，而结晶器压力的影响最小。最佳工艺条件为结晶器压力15MPa、结晶器温度320K、溶液浓度1.2mg/mL、CO/溶液流速比134g/g，得到平均粒径为808nm的姜黄素亚微米颗粒。本研究证明了外部可调环形间隙喷嘴及其相关设备在SAS工艺中的可行性，显示出在减小颗粒尺寸和提高难溶性药物生物利用度方面的巨大潜力。
