Thesis supervisors Senior Research Fellow Karin Kogermann, PhD (Institute of Pharmacy, University of Tartu) and Professor Jyrki Heinämäki, PhD ((Institute of Pharmacy, University of Tartu)).
Opponent Lead Research Fellow Kaisa Naelapää, PhD (pharmacy) (Novo Nordisk, Copenhagen, Denmark).
Many poorly water-soluble active pharmaceutical ingredients (APIs) can exist in different polymorphic or solvated crystal forms and also in the amorphous state. The least stable form of API is an amorphous form, but this state has usually an enhanced solubility, dissolution and bioavailability compared to the crystalline state. The main objectives of this thesis were to investigate the amorphization and physical stabilization of poorly water-soluble model API, piroxicam (PRX), to investigate electrospinning (ES) as a novel technique in fabricating the high-energy amorphous solid dispersions (SDs) of a poorly water-soluble API, to characterize the physicochemical properties of nanofibrous SDs, and to investigate their dissolution behavior. The properties of API and drug-loaded nanofibers were investigated by scanning electron microscopy (SEM), X-ray powder diffraction (XRPD), Raman spectroscopy, differential scanning calorimetry (DSC) and scanning white light interferometry (SWLI). Hydroxypropyl methylcellulose (HPMC) and a new synthetic graft copolymer Soluplus® were investigated as hydrophilic carrier polymers for ES. ES was found to be applicable for the amorphization of PRX and for fabricating the SD type nanofibrous matrices. The physical stability and dissolution of SDs were dependent on the carrier polymer, initial crystalline form of PRX, solvent system and storage conditions applied. Both carrier polymers stabilized the amorphous state of PRX. SWLI was found to be the method of choice for the rapid non-contacting and non-destructive three dimensional surface topographic analysis of nanofibrous mats. The solubility and dissolution rate of amorphous PRX loaded in ES nanofibers were greatly dependent on the physicochemical properties of a carrier polymer.