Crystallization and intermolecular hydrogen bonding in carbamazepine-polyvinyl pyrrolidone solid dispersions: An experiment and molecular simulation study on drug content variation.

Autor: Wang H; State Key Laboratory of Organic-Inorganic Composites, Beijing University of Chemical Technology, Beijing 100029, PR China., Luan Y; State Key Laboratory of Organic-Inorganic Composites, Beijing University of Chemical Technology, Beijing 100029, PR China., Li M; State Key Laboratory of Organic-Inorganic Composites, Beijing University of Chemical Technology, Beijing 100029, PR China., Wu S; State Key Laboratory of Organic-Inorganic Composites, Beijing University of Chemical Technology, Beijing 100029, PR China., Zhang S; College of Physics and Optoelectronic Engineering, Shenzhen University, Shenzhen 518060, PR China. Electronic address: 849203540@qq.com., Xue J; State Key Laboratory of Organic-Inorganic Composites, Beijing University of Chemical Technology, Beijing 100029, PR China. Electronic address: jiajiaxue@mail.buct.edu.cn.
Jazyk: angličtina
Zdroj: International journal of pharmaceutics [Int J Pharm] 2024 Dec 05; Vol. 666, pp. 124769. Date of Electronic Publication: 2024 Sep 26.
DOI: 10.1016/j.ijpharm.2024.124769
Abstrakt: The choice of drug content is a critical factor as far as the solid dispersion is concerned. This investigation aims to build the relationship between the drug content, intermolecular hydrogen bonding and the crystalline of the carbamazepine-polyvinyl pyrrolidone solid dispersion. In this work, the microstructural changes of solid dispersions were investigated using experimental characterization combined with molecular simulation. Experimental investigations demonstrated that increasing the drug content enhances the intermolecular hydrogen bonding between drugs, resulting in the crystalline phase of the drug emerged in the solid dispersion. This negatively affects the solubility and stability of solid dispersions. Molecular simulations were then used to analyze the changes of intermolecular hydrogen bonding at different drug content in the system. It revealed a tenfold increase in drug-drug hydrogen bonding concentration as drug content elevated from 10% to 50%, while the drug-excipient hydrogen bonding concentration decreased by 45%. The correlation analysis proves the significant relationships among the drug content, intermolecular hydrogen bonding, and crystallinity of solid dispersion. Using polynomial fitting analysis, the quantitative relationships between the drug content and crystalline properties were investigated. This study will offer valuable insights into the impact of drug content on the performance of solid dispersion.
Competing Interests: Declaration of competing interest The authors 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 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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