Department of Pharmaceutical Technology, School of Pharmacy, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.
Laboratory of Polymer Chemistry and Technology, Department of Chemistry, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.
Int J Pharm. 2020 Mar 30;578:119121. doi: 10.1016/j.ijpharm.2020.119121. Epub 2020 Feb 5.
The present study evaluates the effect of several pharmaceutical plasticizers on the thermo-physical and physicochemical properties of partially hydrolyzed poly(vinyl alcohol) (PVA) used in fusion-based pharmaceutical formulation processes. Specifically, the effect of mannitol (MAN), sorbitol (SOR), sucrose (SUC), anhydrous citric acid (CA), triethyl citrate (TEC) and low-molecular weight polyethylene glycol (PEG400) on PVA's melting properties, physical state and thermal degradation was evaluated via differential scanning calorimetry (DSC), powder X-ray diffractometry (pXRD) and thermo-gravimetric analysis (TGA). Results showed that the use of MAN, SOR, SUC and PEG400 led to the reduction of PVA's melting onset temperature, while MAN, SUC, CA and SOR were amorphously dispersed within PVA's matrix, and the addition of SUC and CA resulted in significant reduction of PVA's crystallinity. TGA results showed the formation of thermally highly unstable PVA mixtures in the cases of CA and TEC (degradation started from ~150 °C and ~125 °C, respectively), while significant molecular interactions were identified by FTIR in the cases of PVA-MAN, PVA-SOR and PVA-SUC. Hot-stage polarized microscopy (HSM) revealed PVA's melt miscibility only with MAN and SOR, while melt flow index (MFI) measurements showed that the use of MAN, SOR and PEG400 resulted in a significant improvement of PVA's melt flow properties. Finally, MD simulations were in close agreement with the experimental observations, indicating that they can be considered as a promising tool for the theoretical modelling of such systems.
本研究评估了几种医药用增塑剂对用于热熔制药配方过程的部分水解聚乙烯醇（PVA）的热物理和物理化学性质的影响。具体而言，通过差示扫描量热法（DSC）、粉末 X 射线衍射（pXRD）和热重分析（TGA）评估了甘露醇（MAN）、山梨糖醇（SOR）、蔗糖（SUC）、无水柠檬酸（CA）、柠檬酸三乙酯（TEC）和低分子量聚乙二醇（PEG400）对 PVA 的熔融特性、物理状态和热降解的影响。结果表明，MAN、SOR、SUC 和 PEG400 的使用导致 PVA 的熔融起始温度降低，而 MAN、SUC、CA 和 SOR 则无定形地分散在 PVA 的基质中，并且 SUC 和 CA 的添加导致 PVA 的结晶度显著降低。TGA 结果表明，在 CA 和 TEC 的情况下，形成了热稳定性非常差的 PVA 混合物（降解分别从约 150°C 和 125°C 开始），而在 PVA-MAN、PVA-SOR 和 PVA-SUC 的情况下，通过傅里叶变换红外光谱（FTIR）鉴定了显著的分子相互作用。高温偏光显微镜（HSM）显示 PVA 仅与 MAN 和 SOR 具有熔融混溶性，而熔体流动指数（MFI）测量表明，MAN、SOR 和 PEG400 的使用导致 PVA 的熔融流动性能显著提高。最后，MD 模拟与实验观察结果非常吻合，表明它们可以被认为是此类系统理论建模的有前途的工具。
