Department of Pharmaceutics, School of Pharmacy, Center for Nano Drug/Gene Delivery and Tissue Engineering, Jiangsu University, Zhenjiang, 212013, China.
Department of Applied Chemistry and Biochemistry, C. K. Tedam University of Technology and Applied Sciences (CKT-UTAS), UK-0215-5321, Navrongo, Ghana.
AAPS PharmSciTech. 2022 Apr 5;23(4):106. doi: 10.1208/s12249-022-02263-3.
Diosmetin (DIOS) is a functional compound with poor water solubility, bad permeability, and crystal form. Self-microemulsifying drug delivery system (SMEDDS) was an effective formulation to overcome these shortcomings. In this study, liquid SMEDDS was prepared using Capmul® MCM C8 EP/NF, Cremophor EL, and PEG 400 (2:5.6:2.4, w/w/w) as excipients. Then, the novel technology of electrospray solidified liquid SMEDDS and prepared solid SMEDDS for inhibiting crystallization. Polyvinyl pyrrolidone (PVP) was used as carrier to construct DIOS-loaded solid SMEDDS, with polyethylene oxide (PEO) contributing to the formation of regular sphere in the process of spinning. The particle size of solid SMEDDS (194 ± 5 nm) was much bigger than of liquid SMEDDS (25 ± 1 nm), while DIOS-loaded solid SMEDDS showed greater dissolution rates in pH 1.2 and pH 6.8 media through in vitro drug release study. The solid nanoparticles were smooth and uniform from the graph of a scanning electron microscope (SEM). The graph of a transmission electron microscope (TEM) showed that small droplets were loaded in the matrix. Furthermore, DIOS was encapsulated by matrix in amorphous state via differential scanning calorimetry (DSC) and attenuated total reflection Fourier transform infrared (ATR-FTIR). The crystalline of DIOS was not formed in solid SMEDDS due to the characteristic peaks of DIOS disappeared in X-ray diffraction (XRD) pattern. Therefore, the oral bioavailability of DIOS improved significantly compared with liquid SMEDDS (4.27-fold). Hence, solid SMEDDS could improve the solubility and bioavailability of DIOS, through transfer of the state of crystalline to amorphous by electrospray technology.
地奥司明（DIOS）是一种功能化合物，其水溶性差、渗透性差、结晶形式差。自微乳药物传递系统（SMEDDS）是克服这些缺点的有效制剂。在这项研究中，使用 Capmul® MCM C8 EP/NF、Cremophor EL 和 PEG 400（2:5.6:2.4，w/w/w）作为辅料制备液体 SMEDDS。然后，采用静电喷雾固化液体 SMEDDS 新技术和制备抑制结晶的固体 SMEDDS。聚维酮（PVP）用作载体构建载有地奥司明的固体 SMEDDS，其中聚氧化乙烯（PEO）有助于在纺丝过程中形成规则球体。固体 SMEDDS 的粒径（194±5nm）明显大于液体 SMEDDS（25±1nm），而载有地奥司明的固体 SMEDDS 通过体外药物释放研究显示在 pH1.2 和 pH6.8 介质中有更大的溶解速率。扫描电子显微镜（SEM）图谱显示固体 SMEDDS 的颗粒光滑均匀。透射电子显微镜（TEM）图谱显示小液滴装载在基质中。此外，通过差示扫描量热法（DSC）和衰减全反射傅里叶变换红外（ATR-FTIR），地奥司明以无定形态被基质包裹。由于地奥司明的特征峰在 X 射线衍射（XRD）图谱中消失，因此固体 SMEDDS 中未形成地奥司明的晶体。因此，与液体 SMEDDS 相比，地奥司明的口服生物利用度显著提高（提高了 4.27 倍）。因此，通过静电喷雾技术将结晶状态转变为无定形态，固体 SMEDDS 可以提高地奥司明的溶解度和生物利用度。
