Ondřej Kašpar – PhD thesis summary

Investigation of Process-Structure-Property Relationships in Dry Particulate Systems

This work deals with the preparation of composite particles by spray drying and batch wet granulation methods. A similar attribute of both methods was the detailed investigation of the influence input process parameters on the properties of the final product, the development of a robust methodology for the visualization of particle morphology and microstructure, as well as the evaluation of the transport properties.

In the case of spray drying, a unique cross-linking method of chitosan carriers by a 3-fluid kinetic nozzle and spray dryer Büchi B-290 was rigorously investigated. In the first step, the influence of input parameters on the characteristics of the final powder product was analyzed. The determination of optimum values for all input parameters was followed by the encapsulation of particular active substances (silver in the form of nanoparticles and the enzyme laccase). In the case of encapsulation of silver nanoparticles the effect of nozzle type, inlet concentration of silver and presence of water-soluble substance (porogen) in the final formulation on the release kinetics and antibacterial activity was studied. Likewise, in the case of laccase immobilization, the influence of input parameters and the choice of cross-linking method (2 or 3-fluid nozzle) on the final specific enzymatic activity were investigated. The second part of this work deals with the influence of process parameters of batch highshear wet granulation on the segregation of active pharmaceutical ingredient (API), particle size distribution and API release characteristic from granules. A novel methodology for the evaluation of porosity, pore size distribution, pore visualization and pore-connectivity from computer tomography (CT) data by image analysis was established. The gradual dissolution of API crystals in the granule coupled with CT and UV/Vis technique allowed the determination of the effective diffusion coefficient of the API. The connection between porosity and effective diffusion coefficient has been found in the form of the Archie’s law.