Orszulak Luiza, Lamrani Taoufik, Tarnacka Magdalena, Hachuła Barbara, Jurkiewicz Karolina, Zioła Patryk, Mrozek-Wilczkiewicz Anna, Kamińska Ewa, Kamiński Kamil
Institute of Chemistry, Faculty of Science and Technology, University of Silesia in Katowice, Szkolna 9, 40-007 Katowice, Poland.
Institute of Physics, Faculty of Science and Technology, University of Silesia in Katowice, 75 Pułku Piechoty 1A, 41-500 Chorzow, Poland.
Pharmaceutics. 2024 Jan 19;16(1):136. doi: 10.3390/pharmaceutics16010136.
In this paper, we propose one-step synthetic strategies for obtaining well-defined linear and star-shaped polyvinylpyrrolidone (PVP and PVP). The produced macromolecules and a commercial PVP K30 with linear topology were investigated as potential matrices for suppressing metronidazole (MTZ) crystallization. Interestingly, during the formation of binary mixtures (BMs) containing different polymers and MTZ, we found that linear PVPs exhibit maximum miscibility with the drug at a 50:50 weight ratio (/), while the star-shaped polymer mixes with MTZ even at a 30:70 /. To explain these observations, comprehensive studies of MTZ-PVP formulations with various contents of both components were performed using Fourier-transform infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction. The obtained results clearly showed that the polymer's topology plays a significant role in the type of interactions occurring between the matrix and MTZ. Additionally, we established that for MTZ-PVP 50:50 and 75:25 / BMs, linear polymers have the most substantial impact on inhibiting the crystallization of API. The star-shaped macromolecule turned out to be the least effective in stabilizing amorphous MTZ at these polymer concentrations. Nevertheless, long-term structural investigations of the MTZ-PVP 30:70 / system (which is not achievable for linear PVPs) demonstrated its complete amorphousness for over one month.
在本文中,我们提出了一步合成策略来制备结构明确的线性和星形聚乙烯吡咯烷酮(PVP和PVP)。对所制备的大分子以及具有线性拓扑结构的市售PVP K30作为抑制甲硝唑(MTZ)结晶的潜在基质进行了研究。有趣的是,在形成包含不同聚合物和MTZ的二元混合物(BMs)过程中,我们发现线性PVP在50:50重量比(/)时与药物表现出最大的混溶性,而星形聚合物即使在30:70 /时也能与MTZ混合。为了解释这些现象,使用傅里叶变换红外光谱、差示扫描量热法和X射线衍射对两种组分具有不同含量的MTZ - PVP制剂进行了全面研究。所得结果清楚地表明,聚合物的拓扑结构在基质与MTZ之间发生的相互作用类型中起着重要作用。此外,我们确定对于MTZ - PVP 50:50和75:25 /的BMs,线性聚合物对抑制活性药物成分的结晶具有最显著的影响。在这些聚合物浓度下,星形大分子在稳定无定形MTZ方面效果最差。然而,对MTZ - PVP 30:70 /体系(线性PVP无法实现)的长期结构研究表明,其在一个多月内完全保持无定形状态。