Abstract:
Recently, glasses, a subset of amorphous solids, have gained attention in various fields, such as polymer chemistry, optical fibers, and pharmaceuticals. One of their characteristic features, the glass transition temperature (Tg) which is absent in 100% crystalline materials, influences several material properties, such as free volume, enthalpy, viscosity, thermodynamic transitions, molecular motions, physical stability, mechanical properties, etc. In addition to Tg, there may be several other temperature-dependent transitions known as sub-Tg transitions (or β-, γ-, and δ-relaxations) which are identified by specific analytical techniques. The study of Tg and sub-Tg transitions occurring in amorphous solids has gained much attention because of its importance in understanding molecular kinetics, and it requires the combination of conventional and novel characterization techniques. In the present study, three different analytical techniques [modulated differential scanning calorimetry (mDSC), dynamic mechanical analysis (DMA), and dielectric relaxation spectroscopy (DRS)] were used to perform comprehensive qualitative/quantitative characterization of molecular relaxations, miscibility, and molecular interactions present in an amorphous polymer (PVPVA), a model drug (indomethacin, IND), and IND/PVPVA-based amorphous solid dispersions (ASDs). This is the first ever reported DMA study on PVPVA in its powder form, which avoids the contribution of solvent to the mechanical properties when a self-standing polymer film is used. A good correlation between the techniques in determining the Tg value of PVPVA, IND, and IND/PVPVA-based ASDs is established, and the negligible difference (within 10 °C) is attributed to the different material properties assessed in each technique. However, the overall Tg behavior, the decrease in Tg with increase in drug loading in ASDs, is universally observed in all the above-mentioned techniques, which reveals their complementarity. DMA and DRS techniques are used to study the different sub-Tg transitions present in PVPVA, amorphous IND, and IND/PVPVA-based ASDs because these transitions are normally too weak or too broad for mDSC to detect. For IND/PVPVA-based ASDs, both techniques show a shift of sub-Tg transitions (or secondary relaxation peaks) toward the high-temperature region from -140 to -45 °C. Thus, this paper outlines the usage of different solid-state characterization techniques in understanding the different molecular dynamics present in the polymer, drug, and their interactions in ASDs with the integrated information obtained from individual techniques.
摘要:
最近,眼镜,无定形固体的一个子集,在各个领域受到关注,如聚合物化学,光纤,和药物。他们的特征之一,在100%晶体材料中不存在的玻璃化转变温度(Tg),影响几个材料属性,如免费卷,焓,粘度,热力学跃迁,分子运动,物理稳定性,机械性能,等。除了Tg,可能还有几种其他温度相关的转变,称为亚Tg转变(或β-,γ-,和δ弛豫),通过特定的分析技术鉴定。在无定形固体中发生的Tg和亚Tg转变的研究由于其在理解分子动力学方面的重要性而获得了很多关注。它需要传统和新颖的表征技术的结合。在本研究中,三种不同的分析技术[调制差示扫描量热法(mDSC),动态力学分析(DMA),和介电弛豫光谱(DRS)]用于对分子弛豫进行全面的定性/定量表征,混溶性,和无定形聚合物(PVPVA)中存在的分子相互作用,模型药物(吲哚美辛,IND),和IND/PVPVA基无定形固体分散体(ASD)。这是有史以来首次报道的关于粉末形式的PVPVA的DMA研究,当使用自支撑聚合物膜时,这避免了溶剂对机械性能的贡献。确定PVPVATg值的技术之间具有良好的相关性,IND,并建立了基于IND/PVPVA的ASD,可以忽略的差异(在10°C内)归因于每种技术中评估的不同材料特性。然而,整体Tg行为,随着ASD中载药量的增加,Tg降低,在上述所有技术中普遍观察到,这揭示了它们的互补性。DMA和DRS技术用于研究PVPVA中存在的不同的亚Tg转变,无定形IND,和基于IND/PVPVA的ASD,因为这些转变通常太弱或太宽,以至于mDSC无法检测到。对于基于IND/PVPVA的ASD,两种技术均显示亚Tg转变(或次级弛豫峰)向高温区域从-140°C至-45°C的偏移。因此,本文概述了使用不同的固态表征技术来理解聚合物中存在的不同分子动力学,药物,以及它们在ASD中与从各个技术获得的综合信息的相互作用。