In the first part of this work, we examine a continuous cooling crystallization cascade process and explore its optimization, while maintaining the content uniformity of the final solid oral dosage form. To predict the CU of the drug product, models dependent on the PSD and the dosage level of the API present in the final dosage form are employed. A number of optimization objectives are then posed, which include increasing throughput of the API and impact of continuous seeding. The trade-offs observed for each optimization objective are also outlined.
In the second portion of this work, a model-based workflow for the scale-up of filtration is presented. The workflow begins with the estimation of the filtration properties from small scale pressure filter experiments. The cake properties were subsequently employed within a centrifuge model to predict the filtration behavior of the system at plant scale and to optimize the process schedule.
- Part I
- A continuous crystallization process is designed to achieve physical property control subject to drug product quality constraints
- Impacts of processing conditions are considered to broaden the attainable region to meet content uniformity constraints
- Part II
- Small scale pressure filter data is used to estimate filter cake properties
- Cake resistance model developed as a function of particle size distribution of crystalline suspension
- Centrifugal filtration schedule determined
|Christopher Burcham is a Senior Engineering Research Advisor at Eli Lilly and Company. Chris received his PhD from Princeton University in 1998, and a BS from the University of Illinois in 1992, both in Chemical Engineering. His career started at The Dow Chemical Company. In 2002, Chris joined Eli Lilly and currently leads the Particle Design Lab.