Rodríguez Israel, Gautam Ritika, Tinoco Arthur D
Department of Chemistry, University of Puerto Rico Río Piedras, San Juan, PR 00925, USA.
Department of Chemistry, Indian Institute of Technology Kanpur, Kanpur 208016, India.
Biomimetics (Basel). 2020 Dec 30;6(1):1. doi: 10.3390/biomimetics6010001.
Drug development is a decades-long, multibillion dollar investment that often limits itself. To decrease the time to drug approval, efforts are focused on drug targets and drug formulation for optimal biocompatibility and efficacy. X-ray structural characterization approaches have catalyzed the drug discovery and design process. Single crystal X-ray diffraction (SCXRD) reveals important structural details and molecular interactions for the manifestation of a disease or for therapeutic effect. Powder X-ray diffraction (PXRD) has provided a method to determine the different phases, purity, and stability of biological drug compounds that possess crystallinity. Recently, synchrotron sources have enabled wider access to the study of noncrystalline or amorphous solids. One valuable technique employed to determine atomic arrangements and local atom ordering of amorphous materials is the pair distribution function (PDF). PDF has been used in the study of amorphous solid dispersions (ASDs). ASDs are made up of an active pharmaceutical ingredient (API) within a drug dispersed at the molecular level in an amorphous polymeric carrier. This information is vital for appropriate formulation of a drug for stability, administration, and efficacy purposes. Natural or biomimetic products are often used as the API or the formulation agent. This review profiles the deep insights that X-ray structural techniques and associated analytical methods can offer in the development of a drug.
药物研发是一项长达数十年、耗资数十亿美元的投资，且常常受到自身限制。为了缩短药物获批时间，人们将精力集中在药物靶点和药物制剂上，以实现最佳的生物相容性和疗效。X射线结构表征方法推动了药物发现和设计过程。单晶X射线衍射（SCXRD）揭示了疾病表现或治疗效果所涉及的重要结构细节和分子相互作用。粉末X射线衍射（PXRD）提供了一种确定具有结晶性的生物药物化合物不同物相、纯度和稳定性的方法。最近，同步辐射源使人们能够更广泛地研究非晶态或无定形固体。用于确定无定形材料原子排列和局部原子有序性的一项有价值的技术是对分布函数（PDF）。PDF已被用于无定形固体分散体（ASD）的研究。ASD由活性药物成分（API）组成，并以分子水平分散在无定形聚合物载体中的药物。这些信息对于为实现稳定性、给药和疗效目的而合理配制药物至关重要。天然或仿生产品常被用作API或制剂剂。本综述概述了X射线结构技术及相关分析方法在药物研发中所能提供的深刻见解。
