Application of design of experiments for optimizing solvent ratios in ceritinib spherical crystallization

IF 4.3 2区材料科学 Q2 ENGINEERING, CHEMICAL

Particuology Pub Date : 2025-08-21 DOI:10.1016/j.partic.2025.08.009

Iva Zokić , Jasna Prlić Kardum , Mirta Sabol , Valentina Travančić

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Abstract

The granulometric properties of active pharmaceutical ingredients (APIs) have significance in the pharmaceutical industry because they affect the handling of powders and thus the efficiency of their production. Ceritinib, an anaplastic lymphoma kinase inhibitor used in the treatment of non-small cell lung cancer, exhibits platy crystals, which results in low flowability and compressibility and negatively affects its production and pharmaceutical application. Spherical crystallization is a promising method for improving the granulometric properties of APIs by transforming unfavorable particle shapes into a more favorable spherical form.

The aim of this research was to improve the granulometric properties of ceritinib through a combined spherical crystallization method in a system containing tetrahydrofuran as the solvent, water with polyvinylpyrrolidone as the antisolvent, and heptane as the bridging liquid. Experimental design was employed to examine and mathematically describe the influence of the solvent fractions in the selected system on the roundness of the obtained crystals and consequently their compressibility. Spherical crystals of ceritinib with high roundness and improved compressibility compared to powdered ceritinib were obtained. The enhanced powder characteristics facilitate the optimization of the production process, potentially minimizing the necessary number of process steps and increasing efficiency.

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实验设计在头孢替尼球形结晶中优化溶剂配比的应用

活性药物成分（api）的粒度特性在制药工业中具有重要意义，因为它们影响粉末的处理，从而影响其生产效率。Ceritinib是一种用于治疗非小细胞肺癌的间变性淋巴瘤激酶抑制剂，其呈板状晶体，导致流动性和可压缩性低，对其生产和制药应用产生负面影响。球形结晶是一种很有前途的方法，通过将不利的颗粒形状转变为更有利的球形来改善原料药的粒度特性。本研究以四氢呋喃为溶剂，聚乙烯吡罗烷酮为反溶剂，庚烷为桥接液，采用联合球形结晶法改善塞瑞替尼的颗粒性能。采用实验设计来检验和数学描述所选体系中溶剂馏分对所获得晶体的圆度及其可压缩性的影响。获得了高圆度的球形塞瑞替尼晶体，与粉末塞瑞替尼相比，其可压缩性有所提高。增强的粉末特性促进了生产过程的优化，潜在地减少了必要的工艺步骤数量并提高了效率。

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来源期刊

Particuology 工程技术-材料科学：综合

CiteScore

6.70

自引率

2.90%

发文量

1730

审稿时长

32 days

期刊介绍： The word ‘particuology’ was coined to parallel the discipline for the science and technology of particles. Particuology is an interdisciplinary journal that publishes frontier research articles and critical reviews on the discovery, formulation and engineering of particulate materials, processes and systems. It especially welcomes contributions utilising advanced theoretical, modelling and measurement methods to enable the discovery and creation of new particulate materials, and the manufacturing of functional particulate-based products, such as sensors. Papers are handled by Thematic Editors who oversee contributions from specific subject fields. These fields are classified into: Particle Synthesis and Modification; Particle Characterization and Measurement; Granular Systems and Bulk Solids Technology; Fluidization and Particle-Fluid Systems; Aerosols; and Applications of Particle Technology. Key topics concerning the creation and processing of particulates include: -Modelling and simulation of particle formation, collective behaviour of particles and systems for particle production over a broad spectrum of length scales -Mining of experimental data for particle synthesis and surface properties to facilitate the creation of new materials and processes -Particle design and preparation including controlled response and sensing functionalities in formation, delivery systems and biological systems, etc. -Experimental and computational methods for visualization and analysis of particulate system. These topics are broadly relevant to the production of materials, pharmaceuticals and food, and to the conversion of energy resources to fuels and protection of the environment.