To improve the bioavailability of ampicillin trihydrate (AMP) as a poorly water-soluble drug, the nanonization of AMP particles was carried out by solvent anti-solvent precipitation for the first time. In this method the subcritical water (SW) and cold water at ambient conditions were utilized as the solvent and anti-solvent, respectively. At first, the solubility of AMP in SW was measured. The solubility of AMP in SW at a constant pressure of 5 MPa and the temperature range from 303.15 to 403.15 K was found to range from 0.380×10⁻³ to 17.689×10⁻³ mole fractions. The effects of three independent variables, including SW temperature, polyethylene glycol concentration, and anti-solvent temperature, on the particle size and morphology of the precipitated nanoparticles were studied. The obtained results of analyses confirmed that the AMP particles were nanosized to the smallest mean size of 66.5 nm using an environmentally friendly method without the requirement of organic solvents and related post-processing purification stages.

为了提高氨苄青霉素三水合物（AMP）作为水溶性差的药物的生物利用度，首次通过溶剂反溶剂沉淀对AMP颗粒进行纳米化。在该方法中，环境条件下的亚临界水 (SW) 和冷水分别用作溶剂和反溶剂。首先，测量了 AMP 在 SW 中的溶解度。在 5 MPa 的恒压和 303.15 至 403.15 K 的温度范围内，AMP 在 SW 中的溶解度范围为 0.380×10 ^-3至 17.689×10 ^-3摩尔分数。研究了三个自变量，包括 SW 温度、聚乙二醇浓度和反溶剂温度，对沉淀纳米粒子的粒径和形态的影响。获得的分析结果证实，使用环保方法将 AMP 颗粒纳米化至最小平均尺寸 66.5 nm，无需有机溶剂和相关的后处理纯化阶段。