Predictive Drug Release Modeling from Micro-Structural Imaging of Long-Acting Pharmaceutical Devices

For pharmaceutical products, long-acting release formulations that achieve continual drug release over many months or years are desirable for disease prevention and treatment through improvements in patient compliance. A major challenge in the development of these long-acting formulations is that they require lengthy and costly clinical trials. To reduce development timelines, it is of interest to pioneer methods that can preemptively assess the suitability of different formulations to inform on process parameter optimization and batch consistency. To help address these challenges, predictive tools that can generate theoretical drug release profiles are needed. However, drug release from long-acting formulations is mechanistically complex and is mediated not only by composition, but also the macro- and micro-structure of the device. Thus, there is a pressing need to characterize the intricate pharmaceutical structures to enable sophisticated predictive modeling solutions. A novel approach to predictive drug release modeling is presented that combines 3D micro-imaging and diffusional models to simulate drug transport through a pharmaceutical device. An example of an in-line product is discussed and these tools are being applied to guide formulation of development candidate LAPs.