The potential of supramolecular synthon to develop coamorphous systems with tailored physical stability: Mechanistic insights integrating kinetics and thermodynamics.

Autor: Song Y; School of Pharmacy, China Pharmaceutical University, Nanjing 211198, PR China; School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, PR China., Chen Y; School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, PR China., Heng W; School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing 211816, PR China., Hu E; School of Pharmacy, China Pharmaceutical University, Nanjing 211198, PR China., Shi Y; Department of Biology, Emory University, Atlanta, GA 30332, United States., Gao Y; School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, PR China., Zhang J; School of Pharmacy, China Pharmaceutical University, Nanjing 211198, PR China. Electronic address: myamicute@163.com., Wei Y; School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, PR China. Electronic address: weiyuanfengyuer@yeah.net., Qian S; School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, PR China. Electronic address: silence_qs@163.com.
Jazyk: angličtina
Zdroj: International journal of pharmaceutics [Int J Pharm] 2024 Dec 25; Vol. 667 (Pt A), pp. 124857. Date of Electronic Publication: 2024 Oct 21.
DOI: 10.1016/j.ijpharm.2024.124857
Abstrakt: Coamorphous drug delivery systems have received increasing interest owing to their potential to improve the solubility, dissolution and bioavailability of poorly water-soluble drugs. However, the crystallization risk is one of major limitations in their application. It has been widely recognized that the coformer plays a vital role in physical stability of coamorphous formulation. Unfortunately, the screen of optimal coformer still adopts a trial-and-error method, which is time-consuming and expensive. Herein, a supramolecular synthon approach based on the interaction between functional groups, was exploited to design coamorphous systems (CMs) consisting of lurasidone hydrochloride (LH) and three coformers, saccharin (SAC), L-tryptophan (TRP), and L-cysteine hydrochloride (CYS). X-ray powder diffraction suggested the order of physical stability of the coamorphous systems was ranked as LH-CYS CM > LH-TRP CM > LH-SAC CM. The charge-assisted hydrogen bond between LH and coformer was confirmed by infrared spectroscopy and solid-state 13 C NMR. Moreover, structural, electronic, and molecular interaction information, especially hydrogen bonding interactions, were quantified by theoretical calculations, including miscibility calculations, molecular dynamics simulations and quantum chemical calculations. It was revealed that LH-CYS CM exhibited the best miscibility, strongest binding energy and strongest H-bond with partially covalent character, demonstrating the significant role of supramolecular synthon in stabilizing coamorphous formulations. Interestingly, LH-TRP CM, not LH-CYS CM, exhibited the lowest molecular mobility among three coamorphous systems, which was inconsistent with their physical stability. But from thermodynamic perspective, the order of configurational entropy and physical stability of coamorphous systems was completely consistent. We shed light on the comprehensive effects of molecular mobility and configurational entropy on physical stability of coamorphous systems. Importantly, the relationship between supramolecular synthon and kinetic/thermodynamic mechanisms was also discussed, and the positive correlation between configurational entropy and intermolecular interactions was proposed in this paper. Our findings demonstrated the great potential of supramolecular synthon in designing coamorphous systems with tailored physical stability, and further provided a deeper insight into the mechanisms of physical stability of coamorphous systems.
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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