PHARMACEUTICAL HYDRATES
PHARMACEUTICAL HYDRATES
复制标题
DOI：
10.1016/0040-6031(94)01952-d
复制
发表时间：
1995-01-02
影响因子：
3.5
通讯作者：
GRANT, DJW
中科院分区：
文献类型：
--
作者：
KHANKARI, RK;GRANT, DJW
水合物是含有母体化合物（例如，药物或赋形剂的无水化合物）和水的固体加合物。本文只讨论了晶体化学计量水合物，其中水分子的环境表现出各种明确的模式，并强调了药物水合物及其行为。水分子的存在影响分子间的相互作用（影响内能和焓）和结晶无序（熵），从而影响自由能、热力学活性、溶解度、溶解速率、稳定性和生物利用度。此外，许多固态性能被改变，包括机械行为，如压片、研磨和产品性能。在产品开发过程中，水合物的物理化学特性包含在问题流程图中，作为“决策树”的一部分需要回答。药物水合物可以通过多种互补的物理化学方法来表征，其中大多数是众所周知的。本文详细介绍了固体核磁共振光谱、拉曼光谱和等温微量热法对水合物的表征，并考虑了各种药物实例。
A hydrate is a solid adduct containing both the parent compound (e.g., the anhydrate of a drug or excipient) and water. This review discusses only the crystalline stoichiometric hydrates in which the environment of the water molecules exhibits various defined patterns, and emphasizes pharmaceutical hydrates and their behavior. The presence of the water molecules influences the intermolecular interactions (affecting the internal energy and enthalpy) and the crystalline disorder (entropy), and hence influences the free energy, thermodynamic activity, solubility, dissolution rate, stability, and bioavailability. In addition, many solid-state properties are altered, including mechanical behavior, such as tableting, grinding, and product performance. The physicochemical characterization of hydrates is included in a flow chart of questions to be answered as part of a ''decision tree'' during the process of product development. Pharmaceutical hydrates may be characterized by a variety of complementary physicochemical methods most of which are well-known. This review details the characterization of hydrates by solid-state nuclear magnetic resonance spectroscopy, Raman spectroscopy, and isothermal microcalorimetry, and considers a variety of pharmaceutical examples.