Paisana Maria C, Wahl Martin A, Pinto João F
iMed.ULisboa -Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, P-1649-003 Lisboa, Portugal.
Pharmazeutisches Institut, Eberhard Karls Universität Tübingen, Auf der Morgenstelle 8, D-72076 Tübingen, Germany.
J Pharm Sci. 2017 Jul;106(7):1786-1794. doi: 10.1016/j.xphs.2017.03.007. Epub 2017 Mar 16.
The potential of polyethyleneglycol (PEG), polyvinylpyrrolidone (PVP), and hydroxypropylcellulose (HPC) to inhibit the hydration of olanzapine (OLZ) in aqueous environments was assessed. OLZ Form I (OLZ) suspended in water (A) or in aqueous polymer solutions (2%, 0.2%, 0.02%, and 0.002%) (PEG 6000 [B], PEG 40,000 [C], HPC LF [D], or PVP K30 [E]). Filtered samples were analyzed by different techniques (X-ray powder diffraction, Fourier transform infrared spectroscopy, differential scanning calorimetry, H-nuclear magnetic resonance spectroscopy). OLZ hydration showed to be faster in water than in PEG solutions, regardless of the polymer molecular weight. OLZ in D and E suspensions remained anhydrous at concentrations of 2%-0.02%. The NMR measurements revealed that all of these polymers were able to establish hydrogen bonds with the OLZ molecule and increased its saturation solubility, but only D and E showed to increase the wettability of the OLZ particles due to binding of these polymers to the surface of hydrate nuclei/first crystals OLZ crystals. This study provided an insight into the mechanisms of OLZ hydrate protection by polymers. It confirmed the advantage of using PVP K30 or HPC LF in wet granulation in concentrations as low as 0.02% to prevent formation of OLZ hydrates, due to the combined effect of H-bond ability and the strong bonding of these polymers to the surface of the crystals.
评估了聚乙二醇（PEG）、聚乙烯吡咯烷酮（PVP）和羟丙基纤维素（HPC）在水性环境中抑制奥氮平（OLZ）水合作用的潜力。将奥氮平晶型I（OLZ）悬浮于水（A）或聚合物水溶液（2%、0.2%、0.02%和0.002%）中（聚乙二醇6000 [B]、聚乙二醇40000 [C]、低取代羟丙基纤维素 [D] 或聚乙烯吡咯烷酮K30 [E]）。通过不同技术（X射线粉末衍射、傅里叶变换红外光谱、差示扫描量热法、氢核磁共振光谱）对过滤后的样品进行分析。无论聚合物分子量如何，奥氮平在水中的水合作用都比在聚乙二醇溶液中更快。在D和E悬浮液中，浓度为2% - 0.02%时奥氮平保持无水状态。核磁共振测量表明，所有这些聚合物都能够与奥氮平分子形成氢键并增加其饱和溶解度，但只有D和E由于这些聚合物与水合核/奥氮平晶体的第一晶体表面结合而显示出增加了奥氮平颗粒的润湿性。本研究深入了解了聚合物对奥氮平水合物的保护机制。它证实了在湿法制粒中使用低至0.02%浓度的聚乙烯吡咯烷酮K30或低取代羟丙基纤维素来防止奥氮平水合物形成的优势，这归因于氢键能力以及这些聚合物与晶体表面的强结合作用的综合效果。
