Freeze-dried nanocrystal dispersion of novel deuterated pyrazoloquinolinone ligand (DK-I-56-1): Process parameters and lyoprotectant selection through the stability study
Објеката
- Тип
- Рад у часопису
- Верзија рада
- објављена верзија
- Језик
- енглески
- Креатор
- Jelena R. Mitrović, Maja Bjelošević Žiberna, Aleksandar Vukadinović, Daniel E. Knutson, Dishary Sharmin, Aleksandar Kremenović, Pegi Ahlin Grabnar, Odon Planinšek, Dominique Lunter, James M. Cook, Miroslav M. Savić, Snežana D. Savić
- Извор
- European Journal of Pharmaceutical Sciences
- Издавач
- Elsevier BV
- Датум издавања
- 2023
- Сажетак
- 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 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.
- том
- 189
- Број
- -
- почетак странице
- 106557
- број страница
- 12
- doi
- 10.1016/j.ejps.2023.106557
- issn
- 0928-0987
- Subject
- Pharmaceutical Science
- Шира категорија рада
- M20
- Ужа категорија рада
- М21
- Права
- Отворени приступ
- Лиценца
- Creative Commons – CC0 Public Domain
- Формат
Jelena R. Mitrović, Maja Bjelošević Žiberna, Aleksandar Vukadinović, Daniel E. Knutson, Dishary Sharmin, Aleksandar Kremenović, Pegi Ahlin Grabnar, Odon Planinšek, Dominique Lunter, James M. Cook, Miroslav M. Savić, Snežana D. Savić. "Freeze-dried nanocrystal dispersion of novel deuterated pyrazoloquinolinone ligand (DK-I-56-1): Process parameters and lyoprotectant selection through the stability study" in European Journal of Pharmaceutical Sciences, Elsevier BV (2023). https://doi.org/10.1016/j.ejps.2023.106557
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