Pajander Jari Pekka, Matero Sanni, Sloth Jakob, Wan Feng, Rantanen Jukka, Yang Mingshi
Department of Pharmacy, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark.
Pharm Res. 2015 Jun;32(6):1993-2002. doi: 10.1007/s11095-014-1592-z. Epub 2014 Dec 13.
This study aimed to investigate the effect of a model protein on the solid state of a commonly used bulk agent in spray-dried formulations.
A series of lysozyme/mannitol formulations were spray-dried using a lab-scale spray dryer. Further, the surface temperature of drying droplet/particles was monitored using the DRYING KINETICS ANALYZER™ (DKA) with controllable drying conditions mimicking the spray-drying process to estimate the drying kinetics of the lysozyme/mannitol formulations. The mannitol polymorphism and the spatial distribution of lysozyme in the particles were examined using X-ray powder diffractometry (XRPD) and Raman microscopy. Partial Least Squares Discriminant Analysis was used for analyzing the Raman microscopy data.
XRPD results indicated that a mixture of β-mannitol and α-mannitol was produced in the spray-drying process which was supported by the Raman analysis, whereas Raman analysis indicated that a mixture of α-mannitol and δ-mannitol was detected in the single particles from DKA. In addition Raman mapping indicated that the presence of lysozyme seemed to favor the appearance of α-mannitol in the particles from DKA evidenced by close proximity of lysozyme and mannitol in the particles.
It suggested that the presence of lysozyme tend to induce metastable solid state forms upon the drying process.
本研究旨在探究一种模型蛋白对喷雾干燥制剂中常用填充剂固态状态的影响。
使用实验室规模的喷雾干燥器对一系列溶菌酶/甘露醇制剂进行喷雾干燥。此外，使用干燥动力学分析仪（DKA）监测干燥液滴/颗粒的表面温度，通过模拟喷雾干燥过程控制干燥条件，以估算溶菌酶/甘露醇制剂的干燥动力学。采用X射线粉末衍射法（XRPD）和拉曼显微镜对甘露醇的多晶型以及颗粒中溶菌酶的空间分布进行检测。运用偏最小二乘判别分析对拉曼显微镜数据进行分析。
XRPD结果表明，喷雾干燥过程中生成了β-甘露醇和α-甘露醇的混合物，这一结果得到拉曼分析的支持；而拉曼分析表明，在来自DKA的单个颗粒中检测到α-甘露醇和δ-甘露醇的混合物。此外，拉曼映射显示，溶菌酶的存在似乎有利于在来自DKA的颗粒中生成α-甘露醇，颗粒中溶菌酶和甘露醇的紧密相邻证明了这一点。
这表明溶菌酶的存在往往会在干燥过程中诱导形成亚稳态固态形式。
