National Science Foundation - Division of Chemical &Transport Systems ? Particulate & Multiphase Processes Program (1415)
Proposal Number: 0651644 Principal Investigators: Matsoukas, Themis Affiliation: Pennsylvania State Univ University Park Proposal Title: Goali: Multicomponent Population Balance Modeling of Pharmaceutical Granulation
Intellectual Merit Granulation is an industrial unit operation for size enlargement of powdered materials. It typically involves a liquid binder that acts as a bonding agent between particles and produces larger granules to improve flowability, enhance the homogeneous distribution of all components, decrease dustiness and prepare the material for tabletting and subsequent processing. It is in wide industrial use and plays an especially important role in pharmaceutical manufacturing. Drug formulation involves the granulation of an active pharmaceutical ingredient along with an inert excipient in the presence of liquid binder that acts as the coalescing medium and which upon drying provides the cohesive strength of the granule. It is a complex, multiphase, multicomponent process, that remains difficult to scale up and control because of the non-trivial coupling of the many variables that influence the quality of the final product. This project focuses on the development of realistic multicomponent population balance models for granulation that use physically-based agglomeration kernels and are validated against experiments. Simulations of multicomponent granulation with one (or two) excipient(s) and a liquid binder will be conducted using a Monte Carlo method that tracks the evolution of a constant number of granules (constant-N Monte Carlo). Collision rates will be calculated from the kinetic theory of granular flow with corrections obtained from mesoscopic simulations of binder-granule interactions. Simulations will be validated against a series of experiments with four excipients (mannitol, lactose, A-TAB, avicel) using aqueous solutions of hydroxypropyl cellulose as the binder, in a pilot-scale Wurster fluidized bed granulator. In addition to simulation and experiments, theory will be developed to describe the distribution and blending of components when the rate of agglomeration is a function of the granule composition, a dependence which may arise from variations in the amount of binder on the granule surface, or different wetting/spreading properties at the granule/binder interface. This program will result in the formulation of theoretical principles of component-blending by agglomeration and in the development of simulation tools for multicomponent particulate processes. Ultimately, the goal is to couple multicomponent population balances to hydrodynamic models to obtain realistic simulators for granulation.
Broader Impacts This work will be undertaken jointly between Penn State and Merck, and with Imperial College (London) through an unfunded collaboration. The PI on this program has considerable experience with graduate, undergraduate as well as minority and female recruitment. This program will support two graduate students who will be jointly advised by the academic and industrial collaborators. It will provide projects for undergraduate research and senior theses, will enhance the curriculum through development of specialty courses on Particle Technology, and will offer the opportunity to both graduate and undergraduate students to visit and interact with industry.
