A novel energy-efficient way to prepare solid lipid microspheres loaded with nanoscale drugs by combining LLPS and in-situ crystallization--颗粒学报PARTICUOLOGY

Li, S., Wu, D., Yu, H., Huang, X., Wang, N., Wang, T., & Hao, H. (2025). A novel energy-efficient way to prepare solid lipid microspheres loaded with nanoscale drugs by combining LLPS and in-situ crystallization. Particuology, 100, 128-139. https://doi.org/10.1016/j.partic.2025.03.015

A novel energy-efficient way to prepare solid lipid microspheres loaded with nanoscale drugs by combining LLPS and in-situ crystallization

Shuyu Li^{a b}, Di Wu^{a b}, Hui Yu^{a b}, Xin Huang^{a b}, Na Wang^{a b}, Ting Wang^{a b *}, Hongxun Hao ^{a b *}

a National Engineering Research Center of Industrial Crystallization Technology, School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300072, China
b State Key Laboratory of Chemical Engineering, Tianjin University, Tianjin, 30072, China

10.1016/j.partic.2025.03.015

Volume 100, May 2025, Pages 128-139

Received 7 November 2024, Revised 4 March 2025, Accepted 16 March 2025, Available online 27 March 2025, Version of Record 2 April 2025.

E-mail: wang_ting@tju.edu.cn; hongxunhao@tju.edu.cn

Highlights

• In-situ crystallization of APIs within the carrier achieves process integration.

• The process obviates requirement for high-energy equipment.

• Particle dispersion is achieved through droplets generated by LLPS.

• The ND@SLMs feature high drug loading,low toxicity,and uniform dispersion.

Abstract

In this work,API nanoscale drugs loaded onto solid lipid microspheres (ND@SLMs) were successfully prepared by combining in-situ crystallization technology and liquid-liquid phase separation (LLPS). This method is characterized by its low energy consumption and the absence of a requirement for high concentrations of surfactants. Tristearin (SSS) was used as the drug carriers,and fenofibrate (FEN) was used as API to verify the feasibility of this method. Characterization was performed using SEM,PXRD, and DSC, while in-situ Raman and EasyViewer enabled real-time monitoring of the particle formation process. The results show that the obtained Active Pharmaceutical Ingredient (API) nanoscale crystals exhibited uniform distribution in the solid lipid carrier and enhanced release rates compared to the bulk ingredients. API droplets prepared by LLPS adhered to the surface of the FEN + SSS droplets played the role of dispersant. Response surface analysis was employed to analyze the independent variables and their interactions, and the optimum value of the processing parameters was obtained. Finally,the expandability of this method to other hydrophobic drugs was verified by ibuprofen (IBU).

Graphical abstract

Keywords

Energy efficient; In-situ crystallization; Liquid-liquid phase separation; Nanoscale drugs; Solid lipid microparticle

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