Preformulation Designed to Enable Discovery and Assess Developability
Preformulation Designed to Enable Discovery and Assess Developability
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DOI：
10.2174/138620710790596781
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发表时间：
2010-02-01
影响因子：
1.8
通讯作者：
Hageman, Michael J.
中科院分区：
文献类型：
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作者：
Hageman, Michael J.
药物分子的物理化学性质影响体内和体外行为的许多方面。不良的物理化学性质通常会严重阻碍建立可靠的SAR、使用体内模型建立原理证明型研究，并最终导致整个开发生命周期中性能变异性和成本增加;在最坏的情况下，甚至会阻止执行所需的开发计划。了解基本的物理化学性质提供了解剖和去卷积实验观察的基础，以这样的方式，可以在设计阶段影响不良分子性质的修改或缓解，确保设计和选择的分子具有很高的概率，使其通过艰难的开发周期。本综述将讨论关键的理化性质，以及如何评估它们，以及它们如何与所选候选药物的发现能力和最终产品开发能力有关。
Physicochemical properties of drug molecules impact many aspects of both in vivo and in vitro behavior. Poor physicochemical properties can often create a significant impediment to establishing reliable SAR, establishing proof of principle type studies using in vivo models, and eventually leading to added performance variability and costs throughout the development life cycle; in the worst case scenario, even preventing execution of the desired development plan. Understanding the fundamental physicochemical properties provides the basis to dissect and deconvolute experimental observations in such a way that modification or mitigation of poor molecular properties can be impacted at the design phase, insuring design and selection of a molecule which has a high probability of making it through the arduous development cycle. This review will discuss the key physicochemical properties and how they can be assessed and how they are implicated in both discovery enablement and in final product developability of the selected candidate.