This study presents an innovative approach that utilizes polymers with different topologies and properties as potential matrices for the poorly water-soluble active pharmaceutical ingredient piribedil (PBD). We investigated amorphous solid dispersions (ASDs) as well as micellar systems composed of PBD and (i) the commercial amphiphilic copolymer Soluplus, (ii) self-synthesized hydrophilic linear PVP (linPVP), and (iii) self-synthesized hydrophilic star-shaped PVP (starPVP). Differential scanning calorimetry, X-ray diffraction, Fourier-transform infrared, and broadband dielectric spectroscopy were applied to gain comprehensive insights into the thermal and structural properties, intermolecular interactions, global molecular dynamics, and recrystallization of the API from the amorphous PBD-polymer ASDs. The primary objective was to evaluate the impact of the type and topology of macromolecules, as well as the composition of binary formulations, on the physical stability of PBD in the amorphous form, phase transition temperatures, the API's recrystallization rate, and ultimately, the release of drug in the prepared ASDs and micelles. Most importantly, our research led to the discovery of new polymorphic form (II) of PBD that has not been previously described in the scientific literature. We also revealed that ASDs containing hydrophilic PVP polymers exhibit the best performance in stabilizing the amorphous form of the API, with the starPVP systems showing the highest stabilization effect. In contrast, for micellar systems, Soluplus turned out to be the most suitable candidate in terms of forming the self-assembles of the lowest size distribution among all systems. The long-term stability of the amorphous drug in PBD-Soluplus micelles was higher compared to PBD-starPVP ASD. Moreover, an improvement in the bioavailability of the API contained in all tested formulations (binary and micellar systems) was observed, with PBD-starPVP micelles exhibiting the most desirable drug release profile within the polymer matrix, as well as the highest concentration of released drug. The obtained data highlight the crucial role of the type and topology/architecture of the polymer in the design of novel pharmaceutical formulations.

Department of Pharmacognosy and Phytochemistry Faculty of Pharmaceutical Sciences in Sosnowiec Medical University of Silesia in Katowice Jagiellonska 4 41 200 Sosnowiec Poland

Department of Physics Faculty of Science University of Hradec Králové Rokitanského 62 500 03 Hradec Králové Czech Republic

Institute of Chemistry Faculty of Science and Technology University of Silesia in Katowice Szkolna 9 40 006 Katowice Poland

Institute of Materials Engineering University of Silesia in Katowice 75 Pulku Piechoty 1A 41 500 Chorzow Poland

Institute of Physics Faculty of Science and Technology University of Silesia in Katowice 75 Pulku Piechoty 1A 41 500 Chorzow Poland

Physiolution Polska sp z o o Skarbowcow 81 7 53 025 Wroclaw Poland

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