20.500.12556/RUL-148364 Freeze-dried nanocrystal dispersion of novel deuterated pyrazoloquinolinone ligand (DK-I-56-1) process parameters and lyoprotectant selection through the stability study Recently, nanocrystal dispersions have been considered as a promising formulation strategy to improve the bioavailability of the deuterated pyrazoloquinolinone ligand DK-I-56-1 (7-methoxy-2-(4-methoxy-d3-phenyl)-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one). In the current study, the freeze-drying process (formulation and process parameters) was investigated to improve the storage stability of the previously developed formulation. Different combinations of lyoprotectant (sucrose or trehalose) and bulking agent (mannitol) were varied while formulations were freeze-dried under two conditions (primary drying at -10°C or -45°C). The obtained lyophilizates were characterized in terms of particle size, solid state properties and morphology, while the interactions within the samples were analyzed by Fourier transform infrared spectroscopy. In the preliminary study, three formulations were selected based on the high redispersibility index values (around 95%). The temperature of primary drying had no significant effect on particle size, but stability during storage was impaired for samples dried at -10°C. Samples dried at lower temperature were more homogeneous and remained stable for three months. It was found that the optimal ratio of sucrose or trehalose to mannitol was 3:2 at a total concentration of 10% to achieve the best stability (particle size < 1.0 μm, polydispersity index < 0.250). The amorphous state of lyoprotectants probably provided a high degree of interaction with nanocrystals, while the crystalline mannitol provided an elegant cake structure. Sucrose was superior to trehalose in maintaining particle size during freeze-drying, while trehalose was more effective in keeping particle size within limits during storage. In conclusion, results demonstrated that the appropriate combination of sucrose/trehalose and mannitol together with the appropriate selection of lyophilization process parameters could yield nanocrystals with satisfactory stability. pyrazoloquinolinone nanocrystals freeze-drying sucrose trehalose mannitol pirazolokinolinon nanokristali liofilizacija saharoza trehaloza manitol farmacevtske oblike nanomateriali true false true Angleški jezik Slovenski jezik Članek v reviji 2023-08-18 12:14:57 2023-08-18 12:15:00 2023-08-25 12:04:38 0000-00-00 00:00:00 2023 0 0 12 str. Vol. 189, art. 106557 2023 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 66.017-022.513.2:620.3 0928-0987 10.1016/j.ejps.2023.106557 161164291 1-s2.0-S0928098723001872-main.pdf 1-s2.0-S0928098723001872-main.pdf 1 125EBEF51E34FB5A229A6AAE3E163FA8 12d4bbc8367fd0fadb4e125866d48a217d7f007fddddd93364265ffaa2c535c0 27970b6b-3db1-11ee-b9d7-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=172543 https://www.sciencedirect.com/science/article/pii/S0928098723001872 1 13058d1a-3db0-11ee-b9d7-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=172542 Fakulteta za farmacijo 0 0 0