Hoppu Pekka, Hietala Sami, Schantz Staffan, Juppo Anne Mari
Division of Pharmaceutical Technology, University of Helsinki, Finland.
Eur J Pharm Biopharm. 2009 Jan;71(1):55-63. doi: 10.1016/j.ejpb.2008.06.029. Epub 2008 Jul 8.
The aim of this study was to investigate the rheological properties, molecular mobility and crystallization tendency of pure citric acid and paracetamol or blends of them. Amorphous samples were produced by ethanol-evaporation or by melt-quenching. Enthalpy recovery, glass fragility and heat capacity were determined by differential scanning calorimetry (DSC). Other physical characterization methods were rheology and the crystallization tendency using X-ray powder diffraction (XRPD) and DSC. All the samples behaved as Newtonian liquids and they were fragile glasses. The 50/50 (w/w,%) blend had good physical stability upon consecutive shearing regardless of the preparation method. All the samples were stable for at least one year in dry conditions at -20 degrees C. The melt-produced blends containing 25% or 50% paracetamol were stable at least two years in dry ambient conditions. The good physical stability at ambient temperature cannot be explained by molecular mobility because molecular mobility of the model material is less than 100 s in ambient conditions. Thus other factors, such as the thermodynamic and crystallization driving forces or formation of degradation products, must determine the physical stability of the blends. The composition and processing method have an impact on the physical stability of the sample.
本研究的目的是探究纯柠檬酸、对乙酰氨基酚及其混合物的流变学性质、分子流动性和结晶倾向。通过乙醇蒸发或熔融淬火制备非晶态样品。采用差示扫描量热法（DSC）测定焓恢复、玻璃化脆性和热容。其他物理表征方法包括流变学以及使用X射线粉末衍射（XRPD）和DSC的结晶倾向。所有样品均表现为牛顿流体，且为脆性玻璃。无论制备方法如何，50/50（w/w,%）的混合物在连续剪切下具有良好的物理稳定性。所有样品在-20℃干燥条件下至少稳定一年。含25%或50%对乙酰氨基酚的熔融制备混合物在干燥环境条件下至少稳定两年。室温下良好的物理稳定性无法用分子流动性来解释，因为模型材料在环境条件下的分子流动性小于100 s。因此，其他因素，如热力学和结晶驱动力或降解产物的形成，必定决定了混合物的物理稳定性。组成和加工方法对样品的物理稳定性有影响。
