Numerical Tools for Predicting Drug Dissolution Profiles

描述(由申请人提供)：这份STTR第一阶段提案描述了一种建模框架的开发，该框架将流体动力学的介观模型与溶出动力学模型相结合，以便准确地描述药物的溶出行为。药物溶出度问题的复杂性导致了经验方法的发展成为制药行业的普遍做法。然而，由于缺乏机械信息，每个新配方都必须重复这一过程，并且无法从测试中获得任何见解。这一过程增加了成本，并增加了新药上市的时间。我们的方法使用格子Boltzmann模型，并使用创新的模块化方法结合详细的溶出动力学，以便我们可以在现实的流体动力学条件下研究药物的溶出。此外，我们的方法保留了药物的空间信息，因此我们可以研究不同形态(片剂内部成分的排列)对溶出行为的影响。我们计划开发这一方法学，并通过将我们的模型与已发表的关于水杨酸片溶出行为的文献数据进行比较来证明其可行性。该项目是一家在化学建模、燃烧工程和数值模拟方面拥有深厚专业知识的软件公司(RES Group Inc.)和石溪大学(Stony Brook University)的一个理论小组(Gersape)之间的密切合作，该公司在建模方面的专长从微观分子动力学模拟到介观模型，如格子Boltzmann方法和平均场方法。 与公共健康的相关性：这项STTR第一阶段提案描述了一个建模框架的开发，该框架将流体动力学的介观模型与溶出动力学模型相结合，以便准确地描述药物的溶出行为。这项建议旨在通过开发一种基于模型的方法以及相关的工作流程和工具来提高药物溶出度测试的效率，使制药研究人员能够显著降低成本并缩短新药的上市时间。

DESCRIPTION (provided by applicant): This STTR Phase I proposal describes the development of a modeling framework that combines a mesoscopic model for hydrodynamics with dissolution kinetic models in order to accurately describe the dissolution behavior of drugs. The complexities of the drug 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 uses the Lattice Boltzmann model, and uses an innovative modular approach of incorporating the detailed dissolution kinetics such that we can study drug dissolution under realistic hydrodynamic conditions. Further, our approach retains spatial information about the drug, and consequently we can study the effect of different morphologies (arrangement of components inside the tablet) on the dissolution behavior. We plan to develop this methodology and demonstrate its feasibility by comparing our model against published literature data on the dissolution behavior of salicyclic acid tablets. The project is a close collaboration between a software company (RES Group Inc) with deep expertise in chemical modeling, combustion engineering and numerical simulation and a theory group (Gersappe) at Stony Brook University with expertise in modeling ranging from microscopic Molecular Dynamics simulations to mesoscopic models such as the Lattice Boltzmann method and mean field methods. PUBLIC HEALTH RELEVANCE: This STTR Phase I proposal describes the development of a modeling framework that combines a mesoscopic model for hydrodynamics with dissolution kinetic models in order to accurately describe the dissolution behavior of drugs. This proposal aims to improve the efficiency of drug dissolution testing by developing a model based approach, along with associated workflow and tools that will enable pharmaceutical researchers to significantly reduce the cost and improve the time to market for new drugs.