University of Graz, Institute of Pharmaceutical Sciences, Department of Pharmaceutical Technology and Biopharmacy, Universitätsplatz 1, 8010 Graz, Austria.
Central European Research Infrastructure Consortium (CERIC-ERIC), 34149 Basovizza, Trieste, Italy.
Eur J Pharm Biopharm. 2019 Jun;139:153-160. doi: 10.1016/j.ejpb.2019.03.017. Epub 2019 Mar 21.
The development of lipid nanoparticles requires knowledge on the crystalline structure, polymorphic transitions and lipid-drug interactions. This study aimed at introducing advanced techniques to characterize nanostructured lipid carriers (NLC) comprising palmitic acid, oleic acid, stabilizer and Domperidone. Crystallinity of single components and mixtures was investigated by laboratory Small Angle X-ray Scattering (SAXS). NLC were studied with laboratory Small and Wide Angle X-ray Scattering (SWAXS). Photon Correlation Spectroscopy and Freeze Fracture Transmission Electron Microscopy were used to monitor particle size, zeta potential and shape. Stability of NLC was investigated using synchrotron X-ray Diffraction (XRD) and SAXS and laboratory SAXS. Palmitic acid showed a lamellar structure (polymorph C), which was still present after particle preparation. Spherical 300 nm-sized particles with zeta potential values above -30 mV were obtained and Domperidone was incorporated in its amorphous form. During storage, no differences in synchrotron XRD spectra were seen. However, laboratory SAXS measurements showed a second lamellar structure, identified as polymorph B. Synchrotron SAXS temperature scans confirmed that polymorph B did not affect the morphology of the encapsulated drug or the shape of NLC. These results highlight the unique capabilities of laboratory and synchrotron X-ray Scattering and Diffraction for improved structural characterization of lipid nanoparticles.
脂质纳米粒的开发需要了解晶体结构、多晶型转变和脂质-药物相互作用。本研究旨在介绍先进的技术，用于表征包含棕榈酸、油酸、稳定剂和多潘立酮的纳米结构脂质载体（NLC）。通过实验室小角 X 射线散射（SAXS）研究了单一成分和混合物的结晶度。通过实验室小角和广角 X 射线散射（SWAXS）研究了 NLC。光子相关光谱法和冷冻断裂透射电子显微镜用于监测粒径、Zeta 电位和形状。使用同步辐射 X 射线衍射（XRD）和 SAXS 以及实验室 SAXS 研究了 NLC 的稳定性。棕榈酸显示层状结构（多晶型 C），在颗粒制备后仍存在。获得了具有超过-30 mV 的 Zeta 电位值的 300nm 大小的球形颗粒，并将多潘立酮以无定形形式掺入。在储存过程中，未见同步辐射 XRD 光谱有差异。然而，实验室 SAXS 测量显示出第二种层状结构，鉴定为多晶型 B。同步辐射 SAXS 温度扫描证实，多晶型 B 不会影响包封药物的形态或 NLC 的形状。这些结果突出了实验室和同步辐射 X 射线散射和衍射在改善脂质纳米粒结构表征方面的独特能力。
