title: Determination of critical parameters of drug substance influencing dissolution: a case study.
abstract: The purpose of this study was to specify critical parameters (physicochemical characteristics) of drug substance that can affect dissolution profile/dissolution rate of the final drug product manufactured by validated procedure from various batches of the same drug substance received from different suppliers. The target was to design a sufficiently robust drug substance specification allowing to obtain a satisfactory drug product. For this reason, five batches of the drug substance and five samples of the final peroral drug products were analysed with the use of solid state analysis methods on the bulk level. Besides polymorphism, particle size distribution, surface area, zeta potential, and water content were identified as important parameters, and the zeta potential and the particle size distribution of the drug substance seem to be critical quality attributes affecting the dissolution rate of the drug substance released from the final peroral drug formulation.
authors.affiliation: Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences Brno, Palackeho 1/3, 612 42 Brno, Czech Republic.
authors.forename: Erika
authors.initials: E
authors.lastname: Bojnanska
authors.affiliation: Faculty of Chemistry, Brno University of Technology, Purkynova 464/118, 612 00 Brno, Czech Republic.
authors.forename: Michal
authors.initials: M
authors.lastname: Kalina
authors.affiliation: Faculty of Chemistry, Brno University of Technology, Purkynova 464/118, 612 00 Brno, Czech Republic.
authors.forename: Ladislav
authors.identifier: 0000-0003-1516-6399
authors.initials: L
authors.lastname: Parizek
authors.affiliation: Faculty of Chemistry, Brno University of Technology, Purkynova 464/118, 612 00 Brno, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Bartonickova
authors.affiliation: Faculty of Chemistry, Brno University of Technology, Purkynova 464/118, 612 00 Brno, Czech Republic.
authors.forename: Tomas
authors.initials: T
authors.lastname: Opravil
authors.affiliation: Faculty of Chemistry, Brno University of Technology, Purkynova 464/118, 612 00 Brno, Czech Republic.
authors.forename: Michal
authors.initials: M
authors.lastname: Vesely
authors.affiliation: Faculty of Chemistry, Brno University of Technology, Purkynova 464/118, 612 00 Brno, Czech Republic.
authors.forename: Miloslav
authors.initials: M
authors.lastname: Pekar
authors.affiliation: Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences Brno, Palackeho 1/3, 612 42 Brno, Czech Republic.
authors.forename: Josef
authors.identifier: 0000-0003-2003-9052
authors.initials: J
authors.lastname: Jampilek
mesh_terms: D055598:Chemical Phenomena; D065546:Drug Liberation; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D012995:Solubility