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制剂一致性研究中如何提高效率、充分保障仿制制剂与原研药一致,亟待发展新的技术和方法。对于具有结构特征的固体制剂、微粒分散体系,结构是其特定处方与工艺技术的结果,决定其递送药物的释放行为及其体内药代动力学行为。传统表征技术不能对结构进行定量,而同步辐射成像等新一代结构定量表征技术,在揭示制剂内部结构方面展现了前所未有的能力,能定量表征制剂的静态结构和动态结构,实现制剂工艺的逆向工程剖析和制剂间结构异同的甄别。本团队建立了方法学,采用该技术实现了在静态结构(原辅料粉体结构、颗粒单元结构、片剂结构和膜结构等)和水化等动态结构、固体制剂工艺甄别等方面的应用,将制剂的结构划分为从剂型到制剂中间体、动态结构、分子结构等四级结构,提出了基于制剂结构的药物一致性评价新策略。在制剂释药行为一致的基础上,制剂内部精细结构的一致更有助于确保制剂的一致性。
How to improve the efficiency of formulation consistency research and fully guarantee that the generic preparation is consistent with that of the original research drug and there is an urgent need to develop new technologies and methods. For structured formulations of solid formulations, microparticulate dispersions, the structure of which is the result of their specific formulation and processing techniques, determines the release behavior of the delivered drug and its in vivo pharmacokinetic behavior. The traditional characterization technology can not quantify the structure, and the new generation of quantitative structure characterization technique such as synchrotron radiation imaging reveals an unprecedented capability in revealing the internal structure of the preparation, and can quantitatively characterize the static structure and the dynamic structure of the preparation so as to reverse-engineer the preparation process Analysis and preparation of the similarities and differences between the screening. The team has established a methodology, using the technology to achieve the static structure (raw material powder structure, particle structure, tablet structure and membrane structure, etc.) and hydration and other dynamic structure, solid preparation process screening applications, The structure of the formulation is divided into four levels from dosage form to preparation intermediate, dynamic structure and molecular structure, and a new strategy of drug consistency assessment based on formulation structure is proposed. On the basis of consistent release behavior of the preparation, the fine structure of the interior of the preparation is more conducive to ensuring the consistency of the preparation.