Particle size dependence of polymorphism in spray-dried mannitol
Particle size dependence of polymorphism in spray-dried mannitol
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DOI：
10.1016/j.ejps.2011.06.002
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发表时间：
2011-09-18
影响因子：
4.6
通讯作者：
Rantanen, Jukka
中科院分区：
文献类型：
--
作者：
Lee, Yan-Ying;Wu, Jian X.;Rantanen, Jukka
本项目的目的是调查喷雾干燥甘露醇模型配方的多态变化作为颗粒大小的函数。通过调整工艺参数，使用共溶剂和添加模型蛋白(溶菌酶)，制备了不同晶型甘露醇喷雾干燥粉末。使用下一代制药冲击器将获得的干粉分散成不同大小的颗粒。用X射线粉末衍射仪(XRPD)分析了不同粒度组分中甘露醇的晶型。傅里叶变换近红外(FT-NIR)和拉曼光谱。用化学计量学方法对红外光谱和拉曼光谱进行了解析。本研究建立了不同的喷雾干燥甘露醇体系，其中含有α-甘露醇和β-甘露醇的混合物。XRPD、FT-NIR和拉曼光谱研究表明，乙醇作为共溶剂增加了α-甘露醇在较小颗粒中的含量。低水平溶菌酶的加入导致较小颗粒中的α-甘露醇含量增加，而喷雾干燥甘露醇体系中溶菌酶含量的增加导致较小颗粒组分中的β-甘露醇含量增加。总之，甘露醇配方的喷雾干燥会导致甘露醇的固态组成随颗粒大小的变化而变化。这一发现可能与临床相关，并强调需要对喷雾干燥生产的可吸入干粉进行适当的过程控制。(C)2011爱思唯尔B.V.保留所有权利。
The purpose of this project was to investigate the polymorphic variation of spray-dried mannitol model formulations as a function of particle size. Spray-dried powders with varying mannitol polymorphs were produced by adjusting process parameters, using co-solvent and adding a model protein (lysozyme). The obtained dry powders were dispersed into different size fractions using a Next Generation Pharmaceutical Impactor. The mannitol polymorphs in the different size fractions were analyzed using X-ray powder diffraction (XRPD). Fourier transform near infrared (FT-NIR) and Raman spectroscopy. Chemometrics was applied to interpret the FT-NIR and Raman spectra. Different spray-dried mannitol systems were established in this study, which contain mixtures of alpha- and beta-mannitol. The XRPD, FT-NIR and Raman studies showed that the use of ethanol as a co-solvent increased the amount of alpha-mannitol in the smaller particles. The addition of low levels of lysozyme resulted in more alpha-mannitol in the smaller particles, while an increased content of lysozyme in spray-dried mannitol system resulted in more beta-mannitol in the smaller particle size fraction. In conclusion spray-drying of mannitol based formulations can result in variation in the solid state composition of mannitol as a function of particle size. This finding may be clinically relevant and underlines the need for proper process control of inhalable dry powder produced by spray-drying. (C) 2011 Elsevier B.V. All rights reserved.