The use of milling and co-milling procedures for preparation of interactive mixtures

Charles University, Faculty of Pharmacy in Hradec Králové Department of: Pharmaceutical Technology Candidate: Mgr. Jana Jezerská Supervisor: doc. PharmDr. Zdeňka Šklubalová, Ph.D. Consultant: Ing. Jakub Koktan, Ph.D. Title of Doctoral Thesis: Utilization of technological procedures of milling and co-milling in the preparation of interactive mixtures The dissertation thesis is an annotated summary of the publication and research activities of the author, Mgr. Jana Jezerská (maiden name Brokešová). The thesis is focused on the preparation of binary interactive powder mixtures which consist of the micronized drug particles adhered onto the larger particles of an excipient (a carrier). The binary powder mixtures were prepared by mixing and/or co-milling and characterized by granulometric methods; crystallinity (thermal analysis, X-ray powder diffractometry), the flow properties (shear cell, avalanche properties) and the surface energy were evaluated as well. The dissolution rate of model drugs was estimated using a flow-through powder dissolution cell (USP-4). The used statistical model (central composite design) enabled to establish optimal milling conditions in a ball mill (the milling speed, the milling time, the size of milling balls) for five powder carriers. Based on quadratic response surface,..