(64b) Evaluation of Mechanical Properties of Organic Crystals for the Prediction of Breakage during Isolation Processes
- Conference: World Congress on Particle Technology
- Year: 2018
- Proceeding: 8th World Congress on Particle Technology
- Group: Applications of Particle Technology for Pharmaceuticals
- Time: Tuesday, April 24, 2018 - 1:53pm-2:16pm
Namazu et al.  conducted 3-point bending test experiments using an inorganic single crystal (Si) fixed beam in order to evaluate the size effect on the mechanical properties of crystals. It was found that reduction of the crystal size leads to an increase in bending strength. Our group developed a single crystal 2-point bending test by fixing one edge of single microscopic needle-shaped crystals and applying a force at the other edge using Atomic Force Microscopy . We employed this method to determine the micro-mechanical properties of Î²-L-glutamic acid (Î²-LGA), a needle-shaped organic crystal. Similar to , a high number of experiments demonstrated that the yield stress is a strong function of the crystal size. Using a derivative from Bernoulliâs beam theory , it was found that the critical stress leading to Î²-LGA crystal snapping is equal to 13.8 MPa. As the crystals are by nature not identical, a Weibull analysis was also performed to model the distribution of the experimental observations. The Weibullâs distribution function shape (k) and scale (Î») parameters were estimated and are equal to 2.07 and 1.896x107 respectively. The median of the Weibull distribution is equal to 15.9 MPa, meaning that 50% of the crystals would break under such a stress .
A solid mechanics model, implemented in COMSOL Multiphysics, was used to simulate the single crystal fixed beam bending. The model can very accurately predict the crystal deflection and stress profiles under the application of varying forces. The extension of such a model to carry out simulations at the filter bed scale, in conjunction with yield stress experimental findings, could be ultimately used as a predictive tool towards the evaluation of the propensity for particle breakage during API isolation at scale, and the improvement of the process design as well as operating conditions.
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