结构药剂学理论研究: 药物制剂的定量结构及其对药物释放的控制

The release kinetics is the integrated behavior of the dosage form, while the structure basis for the release has not been well investigated. The relation of formulation structure and release control is a fundamental question of pharmaceutics remained to be answered. The high-precision structural information from submicron to millimeter scale can be obtained using powerful facility of synchrotron radiation source to give a CT (Computed Tomography) test to the dosage forms, which brings unprecedented opportunities for the research of the formulation structures. The applicant and his team are one of the pioneers in the structure research of the formulations, and have proposed the structure pharmaceutics theories to catalogue the formulations structure into four levels. In this proposal, aimed at the relation of formulation structures and release control and relayed on the Shanghai Synchrotron Radiation Facility (SSRF), the new technologies of Synchrotron Radiation micro-Computed Tomography (SR-μCT), dynamic CT and Synchrotron Radiation X-ray Fluorescence (SRXF) will be developed to meet the quantitative analysis of the irregular structure, networked structure and dynamic structure of the formulations. Moreover, the spatial distributions of drugs and excipients in the dosage form will be quantitatively evaluated to develop an innovative strategy for the consistency evaluation of the generics. To discover and validate the formulation structure and release control relationship, a new method for the combined in situ structure - composition quantitative analysis technology will be established for the theophylline sustained-release tablets made up of pellets and the dynamic droplet architecture in osmotic pump systems, both of which have typical multi-layered structures. This project aims at new theory of Structure Pharmaceutics, and put forward the pharmaceutics research to a structure-based next level.

释放特征是剂型的整体行为，其结构基础却没有得到充分的研究，“制剂结构-释放控制”关系是尚待探索的药剂学基本问题。应用大科学装置同步辐射光源给制剂做CT，获得亚微米至毫米尺度的高精度结构信息，为制剂结构研究带来前所未有的机遇。申请人团队率先开展制剂结构研究，提出四级结构的结构药剂学理论。本课题针对“制剂结构-释放控制”关系，采用国际先进的上海光源，发展满足制剂结构研究的SR-μCT、动态CT成像、同步辐射X射线荧光成像等新技术，对制剂的不规则结构、网络化结构、动态结构进行定量分析，定量评价药物、辅料在剂型内的空间分布，发展制剂结构一致性评价新方法；针对具有多层次制剂结构的茶碱微丸压制缓释片、动态泡状结构渗透泵制剂，建立制剂原位结构-组成定量分析技术联用新方法，通过制剂结构调控药物释放，发现和验证“制剂结构-释放控制”关系。本课题发展结构药剂学理论，把药剂学研究推向以结构为基础的新层次。

释放特征是剂型的整体行为，其结构基础却没有得到充分的研究，“制剂结构-释放控制”关系是尚待探索的药剂学基本问题。应用大科学装置同步辐射光源给制剂做CT，获得亚微米至毫米尺度的高精度结构信息，为制剂结构研究带来前所未有的机遇。申请人团队率先开展制剂结构研究，提出四级结构的结构药剂学理论。本课题针对“制剂结构-释放控制”关系，采用国际先进的上海光源，发展满足制剂结构研究的SR-μCT、动态CT成像、同步辐射X射线荧光成像等新技术，对制剂的不规则结构、网络化结构、动态结构进行定量分析，定量评价药物、辅料在剂型内的空间分布，发展制剂结构一致性评价新方法；针对具有多层次制剂结构的茶碱微丸压制缓释片、动态泡状结构渗透泵制剂，建立制剂原位结构-组成定量分析技术联用新方法，通过制剂结构调控药物释放，发现和验证“制剂结构-释放控制”关系。本课题发展结构药剂学理论，把药剂学研究推向以结构为基础的新层次。