Effect of Crosslinking on the Properties and Stability of Andrographolide Solid Dispersions.
- 1Key Laboratory of Modern Preparation of Traditional Chinese Medicine, Ministry of Education, Jiangxi University of Chinese Medicine, Nanchang 330004, China.
- 2State Key Laboratory for the Modernization of Classical and Famous Prescriptions of Chinese Medicine, Nanchang 330004, China.
- 3College of Chemistry and Life Sciences, Hubei University of Education, Wuhan 430205, China.
Abstract
Objectives: Crosslinking enhances solid dispersion (SD) stability but often restricts drug release, and this trade-off remains unresolved. In this study, crosslinked polyvinyl alcohol-suberic acid ester (CPSE) carriers with different crosslinking degrees were prepared to investigate the effects of crosslinking on the properties, dissolution and stability of andrographolide (AG)-SDs, aiming to identify crosslinking conditions that ensure both effective dissolution and improved stability. Methods: CPSE was prepared at 110 °C or 130 °C for 4, 8 or 12 h with uncrosslinked polyvinyl alcohol (PVA) as the control. AG-CPSE-SDs and AG-PVA-SD were compared in terms of AG relative crystallinity (RC), surface free energy, hygroscopicity, dissolution and stability. Stability was evaluated after 30-day storage at 40 ± 2 °C/75 ± 5% RH. Results: Compared with AG-PVA-SD, AG-CPSE-SDs showed higher RC but lower surface free energy and hygroscopicity. SDs with lower crosslinking degrees had dissolution profiles similar to AG-PVA-SD, whereas those with higher crosslinking degrees showed significantly reduced dissolution rates. After storage, the dense network in highly crosslinked SDs hindered water entry and diffusion and restricted AG migration and recrystallization, thereby conferring better hygroscopic stability, interaction stability, recrystallization stability and dissolution stability. Notably, the SD using CPSE crosslinked at 130 °C for 4 h as the carrier balanced effective dissolution and enhanced stability. Conclusions: By tuning the crosslinking degree, SD stability can be improved without sacrificing drug dissolution. Moderate rather than maximal crosslinking achieves the optimal balance, providing a practical strategy for designing crosslinked carriers for SDs.
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BibTeX
@article{liu2026effect,
title = {{Effect of Crosslinking on the Properties and Stability of Andrographolide Solid Dispersions.}},
author = {Bingxin Liu and Xinli Liang and Guowei Zhao and Teng Ao and Qiang Zhang and Tangde Feng and Wei Dong},
journal = {Pharmaceutics},
year = {2026},
month = oct,
doi = {10.3390/pharmaceutics18101344},
url = {https://europepmc.org/article/MED/42942873},
note = {CC BY},
}
RIS
TY - JOUR
TI - Effect of Crosslinking on the Properties and Stability of Andrographolide Solid Dispersions.
AU - Bingxin Liu
AU - Xinli Liang
AU - Guowei Zhao
AU - Teng Ao
AU - Qiang Zhang
AU - Tangde Feng
AU - Wei Dong
PY - 2026
DA - 2026/10/21
JO - Pharmaceutics
DO - 10.3390/pharmaceutics18101344
UR - https://europepmc.org/article/MED/42942873
AB - Objectives: Crosslinking enhances solid dispersion (SD) stability but often restricts drug release, and this trade-off remains unresolved. In this study, crosslinked polyvinyl alcohol-suberic acid ester (CPSE) carriers with different crosslinking degrees were prepared to investigate the effects of crosslinking on the properties, dissolution and stability of andrographolide (AG)-SDs, aiming to identify crosslinking conditions that ensure both effective dissolution and improved stability. Methods: CPSE was prepared at 110 °C or 130 °C for 4, 8 or 12 h with uncrosslinked polyvinyl alcohol (PVA) as the control. AG-CPSE-SDs and AG-PVA-SD were compared in terms of AG relative crystallinity (RC), surface free energy, hygroscopicity, dissolution and stability. Stability was evaluated after 30-day storage at 40 ± 2 °C/75 ± 5% RH. Results: Compared with AG-PVA-SD, AG-CPSE-SDs showed higher RC but lower surface free energy and hygroscopicity. SDs with lower crosslinking degrees had dissolution profiles similar to AG-PVA-SD, whereas those with higher crosslinking degrees showed significantly reduced dissolution rates. After storage, the dense network in highly crosslinked SDs hindered water entry and diffusion and restricted AG migration and recrystallization, thereby conferring better hygroscopic stability, interaction stability, recrystallization stability and dissolution stability. Notably, the SD using CPSE crosslinked at 130 °C for 4 h as the carrier balanced effective dissolution and enhanced stability. Conclusions: By tuning the crosslinking degree, SD stability can be improved without sacrificing drug dissolution. Moderate rather than maximal crosslinking achieves the optimal balance, providing a practical strategy for designing crosslinked carriers for SDs.
SN - 1999-4923
ER -