Pfizer Global Research and Development Research Formulations, Cambridge, Massachusetts, 02139, USA.
Lilly Research Laboratories, A Division of Eli Lilly and Company, Indianapolis, Indiana, 46285, USA.
AAPS PharmSciTech. 2018 Jan;19(1):1-10. doi: 10.1208/s12249-017-0849-3. Epub 2017 Jul 28.
This commentary reflects the collective view of pharmaceutical scientists from four different organizations with extensive experience in the field of drug discovery support. Herein, engaging discussion is presented on the current and future approaches for the selection of the most optimal and developable drug candidates. Over the past two decades, developability assessment programs have been implemented with the intention of improving physicochemical and metabolic properties. However, the complexity of both new drug targets and non-traditional drug candidates provides continuing challenges for developing formulations for optimal drug delivery. The need for more enabled technologies to deliver drug candidates has necessitated an even more active role for pharmaceutical scientists to influence many key molecular parameters during compound optimization and selection. This enhanced role begins at the early in vitro screening stages, where key learnings regarding the interplay of molecular structure and pharmaceutical property relationships can be derived. Performance of the drug candidates in formulations intended to support key in vivo studies provides important information on chemotype-formulation compatibility relationships. Structure modifications to support the selection of the solid form are also important to consider, and predictive in silico models are being rapidly developed in this area. Ultimately, the role of pharmaceutical scientists in drug discovery now extends beyond rapid solubility screening, early form assessment, and data delivery. This multidisciplinary role has evolved to include the practice of proactively taking part in the molecular design to better align solid form and formulation requirements to enhance developability potential.
这篇评论反映了四位来自不同组织的药物发现支持领域经验丰富的药物科学家的集体观点。本文就目前和未来选择最佳和可开发药物候选物的方法进行了讨论。在过去的二十年中，已经实施了可开发性评估计划，旨在改善理化性质和代谢性质。然而，新药靶标和非传统药物候选物的复杂性为开发最佳药物递送制剂带来了持续的挑战。为了更有效地输送候选药物，需要更多的使能技术，这使得药物科学家在化合物优化和选择过程中更积极地影响许多关键分子参数。这种增强的作用始于早期的体外筛选阶段，在这个阶段可以从分子结构和药物性质关系的相互作用中获得关键的知识。候选药物在旨在支持关键体内研究的制剂中的性能提供了有关化学型-制剂相容性关系的重要信息。支持选择固体形式的结构修饰也很重要，在这方面，预测性的计算模型正在迅速发展。最终，药物科学家在药物发现中的作用已经超越了快速溶解度筛选、早期形式评估和数据交付。这种多学科的作用已经发展到包括积极参与分子设计的实践，以更好地调整固体形式和制剂要求，提高可开发性潜力。
