College of Pharmaceutical Sciences, Southwest University, Chongqing 400716, China.
Chongqing Academy of Chinese Materia Medica, Chongqing 400065, China.
Molecules. 2021 Mar 23;26(6):1809. doi: 10.3390/molecules26061809.
A drug nanocrystals self-stabilized Pickering emulsion (NSSPE) with a unique composition and microstructure has been proven to significantly increase the bioavailability of poorly soluble drugs. This study aimed to develop a new solid NSSPE of puerarin preserving the original microstructure of NSSPE by spray-drying. A series of water-soluble solid carriers were compared and then Box-Behnken design was used to optimize the parameters of spray-drying. The drug release and stability of the optimized solid NSSPE in vitro were also investigated. The results showed that hydroxypropyl-β-cyclodextrin (HP-β-CD), rather than solid carriers commonly used in solidification of traditional Pickering emulsions, was suitable for the solid NSSPE to retain the original appearance and size of emulsion droplets after reconstitution. The amount of HP-β-CD had more influences on the solid NSSPE than the feed rate and the inlet air temperature. Fluorescence microscopy, confocal laser scanning microscopy and scanning electron microscopy showed that the reconstituted emulsion of the solid NSSPE prepared with HP-β-CD had the same core-shell structure with a core of oil and a shell of puerarin nanocrystals as the liquid NSSPE. The particle size of puerarin nanocrystal sand interfacial adsorption rate also did not change significantly. The cumulative amount of released puerarin from the solid NSSPE had no significant difference compared with the liquid NSSPE, which were both significantly higher than that of puerarin crude material. The solid NSSPE was stable for 3 months under the accelerated condition of 75% relative humidity and 40 °C. Thus, it is possible todevelop the solid NSSPE preserving the unique microstructure and the superior properties in vitro of the liquid NSSPE for poorly soluble drugs.
一种具有独特组成和微观结构的药物纳米晶体自稳定 Pickering 乳液（NSSPE）已被证明可显著提高难溶性药物的生物利用度。本研究旨在通过喷雾干燥开发一种新的葛根素固态 NSSPE，保持 NSSPE 的原始微观结构。比较了一系列水溶性固体载体，然后使用 Box-Behnken 设计优化喷雾干燥参数。还研究了优化的固态 NSSPE 在体外的药物释放和稳定性。结果表明，羟丙基-β-环糊精（HP-β-CD）而不是传统 Pickering 乳液固化中常用的固体载体，适合固态 NSSPE 在再水合后保留乳液液滴的原始外观和大小。HP-β-CD 的量比进料速率和入口空气温度对固态 NSSPE 的影响更大。荧光显微镜、共聚焦激光扫描显微镜和扫描电子显微镜表明，用 HP-β-CD 制备的固态 NSSPE 的再乳液具有与液体 NSSPE 相同的核壳结构，核心为油，外壳为葛根素纳米晶体。纳米晶砂界面吸附率的葛根素粒径也没有明显变化。与液体 NSSPE 相比，固态 NSSPE 中葛根素的累积释放量没有显著差异，均明显高于葛根素粗品。在相对湿度为 75%和 40°C 的加速条件下，固态 NSSPE 稳定 3 个月。因此，有可能为难溶性药物开发保持液体 NSSPE 独特微观结构和体外优异性能的固态 NSSPE。
