The poor aqueous solubility of indapamide (INP) limits its applicability in various biomedical applications. To overcome this issue, nanosized INP particles (INP-HP-β-CD NPs and INP-PVP-K30 NPs) were fabricated using the supercritical antisolvent (SAS) approach to improve the bioavailability of INP. The process, formula, and supercritical antisolvent process were optimized using single-factor and orthogonal methods. The tiny INP-HP-β-CD NPs with a particle size of 142.5 nm and INP-PVP-K30 NPs with a particle size of 150.4 nm were obtained under optimum conditions. Further analysis and characterization, such as SEM, FTIR, XRD, DSC, H NMR, and dissipative particle dynamics (DPD) simulations, were carried out to verify the formation mechanism of the INP complex nanoparticles. The altered physical state of INP from crystalline to amorphous loaded onto the polymer resulted in a significant improvement in the solubility and dissolution rate and high biocompatibility with cells compared to raw INP. Therefore, we propose that INP nanoparticles processed by a supercritical antisolvent process can be used as an advanced drug delivery system, especially for insoluble drugs.

中文翻译：

---

超临界反溶剂技术制备吲达帕胺-HP-β-CD和吲达帕胺-PVP纳米粒子：实验和DPD模拟

吲达帕胺（INP）的水溶性差限制了其在各种生物医学应用中的适用性。为了克服这个问题，使用超临界反溶剂（SAS）方法制备了纳米级 INP 颗粒（INP-HP-β-CD NP 和 INP-PVP-K30 NP），以提高 INP 的生物利用度。采用单因素和正交方法对工艺、配方和超临界反溶剂工艺进行了优化。在最佳条件下获得了粒径为142.5 nm的微小INP-HP-β-CD纳米粒子和粒径为150.4 nm的INP-PVP-K30纳米粒子。进一步的分析和表征，如SEM、FTIR、XRD、DSC、H NMR和耗散粒子动力学（DPD）模拟，验证了INP复合纳米粒子的形成机制。与原始 INP 相比，负载到聚合物上的 INP 从结晶到无定形的物理状态发生改变，导致溶解度和溶出速率显着改善，并且与细胞的生物相容性较高。因此，我们建议通过超临界反溶剂工艺处理的INP纳米颗粒可以用作先进的药物递送系统，特别是对于不溶性药物。