Reducing the size of pharmaceutical particles is an approved way to enhance solubility and bioavailability of a drug, leading to a decrease in the drug dose and its side effects. In this research, nanoparticles of Capecitabine (CPT), an anti-cancer drug, were produced using the gas anti-solvent supercritical (GAS) process. Also, Box–Behnken design (BBD) method was applied to optimize the process condition. Accordingly, the GAS process was performed at different pressures of 120, 140 and 160 bar, temperatures of 308, 318 and 328 K, and solute concentrations of 15, 45 and 75 mg/mL. Based on the size of the precipitated CPT particles, the optimum condition was specified as the pressure of 160 bar, the temperature of 318 K and the initial CPT concentration of 45 mg/mL. Physical identification analysis including differential scanning calorimetry (DSC), X-ray diffraction (XRD), scanning electron microscopy (SEM), dynamic light scattering (DLS), Fourier transform infrared spectrometry (FTIR) and high pressure liquid chromatography (HPLC) analyses were employed to characterize the produced CPT nanoparticles. Significant size reduction of drug particles from 25 μm on average (original) to about 243.3 nm and uniform structure of obtained nanoparticles with a narrow size distribution indicate the effectiveness of the GAS process. Results of the physical analysis confirm the purity of CPT structure with no changes during the GAS process. Also, according to the results of DSC and XRD, the crystallinity of CPT nanoparticles was lower than that of the original sample, leading to higher solubility. Improved CPT solubility was also confirmed by comparison of the dissolution rate of the original and obtained CPT samples in optimum conditions.

减小药物颗粒的尺寸是增强药物溶解度和生物利用度的公认方法，从而导致药物剂量及其副作用的减少。在这项研究中，使用气体反溶剂超临界（GAS）工艺生产了抗癌药物卡培他滨（CPT）的纳米颗粒。此外，还采用了Box–Behnken设计（BBD）方法来优化工艺条件。因此，在120、140和160 bar的不同压力，308、318和328 K的不同压力以及15、45和75 mg / mL的溶质浓度下进行了GAS工艺。根据沉淀的CPT颗粒的大小，将最佳条件指定为160 bar的压力，318 K的温度和45 mg / mL的CPT初始浓度。物理识别分析，包括差示扫描量热法（DSC），使用X射线衍射（XRD），扫描电子显微镜（SEM），动态光散射（DLS），傅里叶变换红外光谱（FTIR）和高压液相色谱（HPLC）分析来表征所生产的CPT纳米粒子。药物颗粒从25种显着减小平均（原始）μm至约243.3 nm，并且所获得的纳米粒子具有窄的尺寸分布，其结构均匀，表明GAS工艺的有效性。物理分析结果证实了CPT结构的纯度，并且在GAS过程中没有任何变化。而且，根据DSC和XRD的结果，CPT纳米颗粒的结晶度低于原始样品的结晶度，从而导致更高的溶解度。通过比较原始和获得的CPT样品在最佳条件下的溶解速度，也可以确认CPT溶解度得到了改善。