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工程化胃滞留型阿魏酸无定形基质:一种提高生物利用度的新型筏状形成模式。

Engineered gastroretentive amorphous ferulate matrix: a novel raft-forming paradigm for enhanced bioavailability.

作者信息

Wiwattanapatapee Ruedeekorn, Chavasiri Nattawat, Laohawiriyakamon Kijja, Pumjan Saravoot, Leelakanok Nattawut, Petchsomrit Arpa

机构信息

Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla, Thailand.

Department of Phytomedicine and Pharmaceutical Biotechnology Excellence Research Center, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla, Thailand.

出版信息

Pharm Dev Technol. 2025 Jul;30(6):875-890. doi: 10.1080/10837450.2025.2525265. Epub 2025 Jun 28.

DOI:10.1080/10837450.2025.2525265
PMID:40566977
Abstract

This study aimed to enhance the solubility of ferulic acid using solid dispersion techniques and develop chewable tablets that neutralize stomach acid, form a protective gel layer, prevent gastric fluid reflux, and ensure prolonged retention in the stomach with controlled release of the active ingredient. Researchers developed solid dispersions of ferulic acid using Eudragit E PO as a carrier, with a 1:2 w/w ratio, achieving the highest solubility (39.9 mg/mL). Chewable tablets were formulated by direct compression, incorporating sodium alginate as a gelling agent, calcium carbonate for calcium ions and carbon dioxide, HPMC as a release retardant, and mannitol as a diluent. All formulations rapidly formed a gel layer within 10 s, had a lower density than gastric fluid, and floated on 0.1 N hydrochloric acid for over 8 h. The optimal formulation demonstrated excellent physical properties, including a gel strength of 11.84 g, an acid neutralization capacity of 15.97 mEq, and reaching 80.58% over 8 h with gradual release. It exhibited significant antioxidant activity (IC 6.74 µg/mL) in the DPPH assay and showed stronger anti-inflammatory effects in macrophage cells than indomethacin. These findings suggest this formulation could enhance ferulic acid's effectiveness in treating gastric ulcers and preventing acid reflux.

摘要

本研究旨在利用固体分散技术提高阿魏酸的溶解度,并开发可咀嚼片,该片剂可中和胃酸、形成保护凝胶层、防止胃液反流,并确保活性成分在胃中长时间滞留并控释。研究人员以Eudragit E PO为载体,以1:2 w/w的比例制备了阿魏酸的固体分散体,实现了最高溶解度(39.9 mg/mL)。通过直接压片制备可咀嚼片,加入海藻酸钠作为胶凝剂、碳酸钙用于提供钙离子和二氧化碳、羟丙基甲基纤维素作为释放阻滞剂以及甘露醇作为稀释剂。所有制剂在10秒内迅速形成凝胶层,密度低于胃液,并在0.1 N盐酸中漂浮超过8小时。最佳制剂表现出优异的物理性质,包括凝胶强度为11.84 g、酸中和能力为15.97 mEq,并在8小时内逐渐释放达到80.58%。在DPPH测定中,它表现出显著的抗氧化活性(IC 6.74 μg/mL),并且在巨噬细胞中显示出比吲哚美辛更强的抗炎作用。这些发现表明该制剂可以提高阿魏酸治疗胃溃疡和预防胃酸反流的效果。

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