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Approaches to understand the solution state organization of spray dried dispersion feed solutions and its translation to the solid state.
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2020-09-23 , DOI: 10.1021/acs.molpharmaceut.0c00729 Matthew K Defrese 1 , Matthew A Farmer 2 , Yuhan Long 3 , Lucas R Timmerman 3 , Younsoo Bae 1 , Patrick J Marsac 1
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2020-09-23 , DOI: 10.1021/acs.molpharmaceut.0c00729 Matthew K Defrese 1 , Matthew A Farmer 2 , Yuhan Long 3 , Lucas R Timmerman 3 , Younsoo Bae 1 , Patrick J Marsac 1
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It is well established that polymers adopt a range of conformations and solution-state organization in response to varying solution environments, although very little work has been done to understand how these effects might impact the physical stability and bioavailability of spray-dried amorphous dispersions (SDDs). Potentially relevant solution-state polymer-solvent/cosolute interactions include preferential solvation, hydrodynamic size (i.e., polymer swelling or collapse), and solvent quality effects (i.e., attractive or repulsive self-interactions). Of particular interest is the investigation of preferential solvation, defined as the relative attraction or rejection of a cosolvent and/or cosolute from the local environment of a solvated macromolecule, which often occurs in multicomponent macromolecular solutions. As spray drying and other solvent-based dispersion processing necessitates the use of complex media consisting of at least three or more components (drug, polymer, solvent(s), and other possible excipients), the prevalence of this phenomenon is likely. This work characterizes largely unexplored solution-state properties in model spray-dried dispersion feed solutions using light scattering and viscometric techniques to add greater context and guidance in studying these information-rich materials. These systems are found to exhibit complex non-intuitive behavior, which serves to highlight the potential utility of preferential solvation in spray-dried dispersion processing and stability. It is hypothesized that solution-state organization of the liquid feed can be engineered and translated to the solid-state for the optimization of SDD properties.
中文翻译：
了解喷雾干燥分散进料溶液的溶液状态组织及其转化为固态的方法。
众所周知，聚合物采用一系列构象和溶液状态组织来响应不同的溶液环境，尽管很少有人了解这些影响如何影响喷雾干燥无定形分散体 (SDD) 的物理稳定性和生物利用度。 ）。潜在相关的溶液状态聚合物-溶剂/共溶质相互作用包括优先溶剂化、流体动力学尺寸（即聚合物溶胀或塌陷）和溶剂质量效应（即吸引或排斥的自相互作用）。特别令人感兴趣的是对优先溶剂化的研究，定义为共溶剂和/或共溶质从溶剂化大分子的局部环境中的相对吸引或排斥，这通常发生在多组分大分子溶液中。由于喷雾干燥和其他基于溶剂的分散处理需要使用由至少三种或更多成分（药物、聚合物、溶剂和其他可能的赋形剂）组成的复杂介质，因此这种现象很可能普遍存在。这项工作使用光散射和粘度测量技术在模型喷雾干燥分散进料溶液中表征了很大程度上未探索的溶液状态特性，以在研究这些信息丰富的材料时增加更多的背景和指导。发现这些系统表现出复杂的非直观行为，这有助于突出优先溶剂化在喷雾干燥分散加工和稳定性中的潜在效用。假设液体进料的溶液状态组织可以设计并转化为固态，以优化 SDD 特性。
更新日期：2020-09-23
中文翻译：
了解喷雾干燥分散进料溶液的溶液状态组织及其转化为固态的方法。
众所周知，聚合物采用一系列构象和溶液状态组织来响应不同的溶液环境，尽管很少有人了解这些影响如何影响喷雾干燥无定形分散体 (SDD) 的物理稳定性和生物利用度。 ）。潜在相关的溶液状态聚合物-溶剂/共溶质相互作用包括优先溶剂化、流体动力学尺寸（即聚合物溶胀或塌陷）和溶剂质量效应（即吸引或排斥的自相互作用）。特别令人感兴趣的是对优先溶剂化的研究，定义为共溶剂和/或共溶质从溶剂化大分子的局部环境中的相对吸引或排斥，这通常发生在多组分大分子溶液中。由于喷雾干燥和其他基于溶剂的分散处理需要使用由至少三种或更多成分（药物、聚合物、溶剂和其他可能的赋形剂）组成的复杂介质，因此这种现象很可能普遍存在。这项工作使用光散射和粘度测量技术在模型喷雾干燥分散进料溶液中表征了很大程度上未探索的溶液状态特性，以在研究这些信息丰富的材料时增加更多的背景和指导。发现这些系统表现出复杂的非直观行为，这有助于突出优先溶剂化在喷雾干燥分散加工和稳定性中的潜在效用。假设液体进料的溶液状态组织可以设计并转化为固态，以优化 SDD 特性。
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