Numerical Tools for Predicting Drug Dissolution Profiles

项目摘要：预测药物溶出曲线的数值工具 该STTR第二阶段提案描述了建模框架的开发， 将流体力学的介观模型与崩解和溶解相结合， 动力学模型，以准确描述片剂的溶出行为。的 片剂溶出问题的复杂性导致了经验的发展， 方法是制药行业的普遍做法。然而，在这方面， 由于缺乏机械信息， 配方，并且不能从测试中获得任何见解。这个过程增加了成本 并增加新药上市的时间。 我们的方法建立在我们的第一阶段方法的基础上，在第一阶段中，我们使用了晶格玻尔兹曼方法。 模型，并开发了一种创新的模块化方法， 溶出动力学，这样我们就可以研究片剂的溶出度。为此，我们计划 包括更现实机制，如融入我们的框架。我们将 包括片剂内部结构的详细信息：其孔隙率、弯曲度和 组件的分布。液体吸收将通过包括毛细管效应来建模， 和材料特性，如润湿性和表面能将包括在我们的 模型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，这样他们就可以确定片剂中的潜在问题， 公式化。

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.