The morphology and stability of amorphous nanoparticles of glibenclamide (GLB) prepared by the antisolvent method using different methods of adding hypromellose (HPMC) were evaluated. Nano-A was prepared by the injection of a dimethyl sulfoxide (DMSO) solution of GLB into the HPMC solution, whereas nano-B was obtained by the injection of a DMSO solution of GLB and HPMC into water. Cryogenic transmission electron microscopy, field-emission scanning electron microscopy, and field-emission transmission electron microscopy, including energy dispersive X-ray spectrometry, revealed that the particles of the nano-A and nano-B samples are hollow spheres and nonspherical nanoparticles, respectively. Powder X-ray diffraction and solid-state NMR measurements showed that GLB is present in an amorphous state in both nano-A and nano-B. The weight ratios of HPMC in the GLB/HPMC nanoparticles were 11 and 16% for nano-A and nano-B, respectively, as determined by solution-state NMR. The glass transition temperatures (T_g) of nano-A and nano-B evaluated using differential scanning calorimetry were lower by about 10 °C compared to that of amorphous GLB, presumably because of a T_g confinement effect and the surface coverage and mixing of HPMC, as suggested by the inverse gas chromatography experiment. GLB crystallization during storage was suppressed more strongly in nano-B than nano-A, owing to the higher amount of HPMC and the higher miscibility between GLB and HPMC. It is suggested that the diffusion rate of the solvent during nanoprecipitation determined the nanoparticle properties. In nano-A, the precipitation of GLB first occurred at the outer interface because of the rapid diffusion of the solvent. Thus, hollow spherical particles with HPMC preferentially located near the surface were formed. On the other hand, the diffusion of the solvent in nano-B was suppressed because of the presence of HPMC, yielding small nonspherical nanoparticles with a high miscibility of GLB and HPMC.

中文翻译：

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用反溶剂法制备的两种不同的格列本脲/羟丙甲纤维素无定形纳米粒子的形态和理化评价

评价了使用不同的添加羟丙甲纤维素（HPMC）方法的反溶剂法制备的格列本脲（GLB）非晶纳米颗粒的形貌和稳定性。通过将GLB的二甲基亚砜（DMSO）溶液注入HPMC溶液来制备Nano-A，而通过将GLB和HPMC的DMSO溶液注入水中获得nano-B。低温透射电子显微镜，场发射扫描电子显微镜和场发射透射电子显微镜（包括能量色散X射线光谱法）显示，纳米A和纳米B样品的颗粒分别是空心球和非球形纳米颗粒。粉末X射线衍射和固态NMR测量表明，GLB在纳米A和纳米B中均以非晶态存在。如通过溶液态NMR测定的，对于纳米A和纳米B，GLB / HPMC纳米颗粒中HPMC的重量比分别为11％和16％。玻璃化温度（使用差示扫描量热法评估的nano-A和nano-B的T _g）比非晶态GLB降低了约10°C，这可能是由于T _g反相气相色谱实验表明，HPMC的限制作用，表面覆盖和混合。由于HPMC的含量较高，且GLB与HPMC之间的混溶性较高，因此在nano-B中，纳米B中的存储过程中GLB结晶受到的抑制要强于nano-A。建议在纳米沉淀过程中溶剂的扩散速率决定了纳米颗粒的性能。在纳米A中，由于溶剂的快速扩散，GLB的沉淀首先出现在外界面。因此，形成了具有优先位于表面附近的HPMC的中空球形颗粒。另一方面，由于HPMC的存在，抑制了溶剂在纳米B中的扩散，得到了具有GLB和HPMC的高混溶性的小的非球形纳米颗粒。