Document Type
Dissertation
Date of Award
5-31-2020
Degree Name
Doctor of Philosophy in Chemical Engineering - (Ph.D.)
Department
Chemical, Biological and Pharmaceutical Engineering
First Advisor
Rajesh N. Dave
Second Advisor
Ecevit Atalay Bilgili
Third Advisor
Edward L. Dreyzin
Fourth Advisor
Murat Guvendiren
Fifth Advisor
Zafar Iqbal
Abstract
Size reduction, an important step in particle engineering, leads to downstream processing problems because of fine powders are cohesive. This research aims to improve the fine particle properties through surface modification and develop better understanding of such processes by model-based analysis. Four case studies concerning surface modification are systematically investigated.
First, enhancement of dissolution behavior of griseofulvin is investigated via combination of amorphization and particle size reduction. The dissolution behavior is affected by the particle size and polymer loading. Finest size amorphous solid dispersions dissolve fast enough to negate the higher recrystallization rate and enhance drug loading by reducing the amount of polymer. Second, enhancing the tableting ability and delaying the release of cohesive and irritative ibuprofen powder are investigated via continuous solventless coating process. The bulk density and flowability of ibuprofen are improved via the surface modification, only 12% of ibuprofen is released in 5 minutes demonstrating the potential for taste masking of active pharmaceutical ingredients. Release mechanism of ibuprofen switches from the anomalous to near zero-order release. Third, the improvement of coating efficiency in high intensity dry powder coating process is examined using an analytical model considering the effects of material stiffness, particle size and mixing intensity. The results show that the coating quality improvs with the decrease of guest particle size and stiffness. The micro-sized guest particles detach from the host particles above 30 Gs, indicating the mixing intensity should be controlled at less than the critical value. Last, optimization of high intensity vibration based cohesive particle mixing process is investigated via DEM simulation. The results and analytical model show that the mixing performance is affected by processing intensity and powder cohesion. The best mixing performance could be observed when the pull-off force equals to the collision shear force.
In summary, the processes and performance of particle engineering via surface modification methods are systematically investigated by model-based analysis along with experimental verification. The relationships between dissolution or mixing performance and its influencing factors such as material property, particle size, mixing intensity, are evaluated. The outcomes are expected to help towards understanding and designing of particle modification processes.
Recommended Citation
Zheng, Kai, "Particle engineering via surface modification: model based analysis" (2020). Dissertations. 1912.
https://digitalcommons.njit.edu/dissertations/1912
