Freeze-dried nanocrystal dispersion of novel deuterated pyrazoloquinolinone ligand (DK-I-56-1): Process parameters and lyoprotectant selection through the stability study
Rattachement africain : rs, si, us, de. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
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.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Freeze-dried nanocrystal dispersion of novel deuterated pyrazoloquinolinone ligand (DK-I-56-1): Process parameters and lyoprotectant selection through the stability study
- Date Crossref
- 01/10/2023
- Éditeur
- Elsevier BV
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
-
University of Belgrade Department of Pharmaceutical Technology and Cosmetology pays non établi dans la noticeUniversité ou école supérieure
-
University of Ljubljana Department of Pharmaceutical Technology pays non établi dans la noticeUniversité ou école supérieure
-
Institute of Physics Belgrade pays non établi dans la noticeStructure de recherche
-
University of Wisconsin–Milwaukee pays non établi dans la noticeUniversité ou école supérieure
-
University of Tübingen pays non établi dans la noticeUniversité ou école supérieure
-
University of Belgrade – Faculty of Pharmacy pays non établi dans la noticeUniversité ou école supérieure
-
University of Wisconsin-Milwaukee Department of Chemistry and Biochemistry pays non établi dans la noticeUniversité ou école supérieure
-
Faculty of Mining and Geology Laboratory of Crystallography pays non établi dans la noticeUniversité ou école supérieure
-
Eberhard-Karls University Institute of Pharmaceutical Technology pays non établi dans la noticeUniversité ou école supérieure
Department of Pharmaceutical Technology and Cosmetology — University of Belgrade, Department of Pharmaceutical Technology — University of Ljubljana et Institute of Physics Belgrade, avec 6 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.