Mechanisms of dissolution and crystallization of amorphous glibenclamide.

Autor: Petkov V; Department of Chemical and Pharmaceutical Engineering, Faculty of Chemistry and Pharmacy, Sofia University, 1 James Bourchier ave., 1164 Sofia, Bulgaria., Vinarov Z; Department of Chemical and Pharmaceutical Engineering, Faculty of Chemistry and Pharmacy, Sofia University, 1 James Bourchier ave., 1164 Sofia, Bulgaria. Electronic address: zv@lcpe.uni-sofia.bg., Tcholakova S; Department of Chemical and Pharmaceutical Engineering, Faculty of Chemistry and Pharmacy, Sofia University, 1 James Bourchier ave., 1164 Sofia, Bulgaria.
Jazyk: angličtina
Zdroj: International journal of pharmaceutics [Int J Pharm] 2024 Dec 05; Vol. 666, pp. 124820. Date of Electronic Publication: 2024 Oct 16.
DOI: 10.1016/j.ijpharm.2024.124820
Abstrakt: Amorphous solid dispersions enhance the dissolution and oral bioavailability of poorly water-soluble drugs. However, the link between polymer properties and formulation performance has not been fully clarified yet. We studied the effect of hydroxypropyl cellulose (HPC) polymers molecular weight (M w ) on the storage stability, dissolution kinetics and supersaturation stability of spray-dried amorphous glibenclamide (GLB) formulations. The solid-state stability of amorphous GLB during storage was significantly enhanced by both the 40 kDa (HPC-SSL) and 84 kDa (HPC-L) polymers, regardless of M w differences. In contrast, HPC-SSL maintained significantly higher aqueous drug concentrations during dissolution, compared to HPC-L (its higher M w analogue). Dedicated dissolution experiments, in situ optical microscopy and solid-state characterization revealed that aqueous drug concentrations were determined by the interplay between crystallization inhibition, drug ionization, wetting and solubilization effects: (1) HPC prevents surface nucleation, hence inhibiting crystallization, (2) intestinal colloids (bile salts and phospholipids) increase supersaturated drug concentrations via wetting and solubilization effects and (3) pH and drug ionization severely impact the degree of supersaturation. The better performance of the lower M w HPC-SSL was due to its superior inhibition of surface crystallization during dissolution. These insights into the molecular mechanisms of dissolution and crystallization of amorphous solids provide foundation for rational formulation development.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Zahari Vinarov reports financial support was provided by Bulgarian National Science Fund. Vladimir Petkov reports equipment, drugs, or supplies was provided by European Union. Slavka Tcholakova reports financial support was provided by European Union. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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