Numerical Tools for Predicting Drug Dissolution Profiles

项目总结：预测药物溶出度的数值工具 该STTR第二阶段提案描述了建模框架的开发，该框架 将流体动力学的介观模型与解体和溶解相结合 动力学模型，以准确描述片剂的溶出行为。这个 片剂溶出度问题的复杂性导致了经验性的发展 方法学是制药业的普遍做法。然而， 由于缺乏机械信息，因此必须为每个新的 公式，从测试中得不到任何见解。这一过程增加了成本 并增加了新药上市的时间。 我们的方法建立在第一阶段方法的基础上，其中我们使用了格子Boltzmann 模型，并开发了一种创新的模块化方法，将详细的 溶出动力学，以便我们可以研究片剂的溶出度。在这项努力中，我们计划 将更现实的机制，如解体纳入我们的框架。我们会 包括有关平板电脑内部结构的详细信息：其多孔性、曲折性和 组件的分布。液体吸收将通过包括毛细效应来建模， 材料属性，如润湿性和表面能，将包括在我们的 模特。其目标是开发一种可供制药研究人员使用的模型 和配方科学家，这样他们就可以识别平板电脑中的潜在问题 配方。

Project Summary: Numerical Tools for Predicting Drug Dissolution Profiles This STTR Phase II proposal describes the development of a modeling framework that combines a mesoscopic model for hydrodynamics with disintegration and dissolution kinetic models in order to accurately describe the dissolution behavior of tablets. The complexities of the tablet dissolution problem have led to the development of empirical methodologies being the widespread practice in the pharmaceutical industry. However, because of a lack of mechanistic information the process has to be repeated for each new formulation, and no insights can be gained from the test. This process adds to the cost and increases the time to market for new drugs. Our approach builds on our Phase I approach, where we used the Lattice Boltzmann model, and developed an innovative modular approach of incorporating the detailed dissolution kinetics such that we could study tablet dissolution. In this effort, we plan to include more realistic mechanisms such as disintegration into our framework. We will include details about the internal structure of the tablet: its porosity, tortuosity, and distribution of components. Liquid uptake will be modeled by including capillary effects, and material properties, such as wettabilities and surface energies will be included in our model. The goal is to develop a model that can be used by pharmaceutical researchers and formulation scientists, such that they can identify potential problems in tablet formulation.