目的 研究阿拉伯半乳糖(AG)作为一种新型多糖类载体在固体分散体制剂中的应用,选用难溶性的白藜芦醇(RES)为模型药物,制备白藜芦醇-阿拉伯半乳糖固体分散体(RES-AG SD)并进行评价。方法 以AG为载体,采用溶剂法制备RES-AG SD,运用差示扫描量热法(DSC)、X射线粉末衍射法(XRPD)、傅里叶变换红外光谱(FTIR)和电子扫描显微镜(SEM)分析方法对其微观结构进行表征和分析,选用浆法研究原料药及RES-AG SD在pH 1.2盐酸溶液及pH 6.8磷酸盐缓冲液中的溶出情况;并对其初步稳定性进行评价。结果 SEM观察发现RES-AG SD呈细碎的不规则颗粒状,RES和AG的形貌特征已不见;DSC、XRPD和FTIR结果显示,RES晶型被破坏,晶体衍射峰基本消失,药物以无定形形态分散于载体AG中,药物与载体之间存在一定的相互作用;体外溶出实验表明,2 h时,RES在2种溶出介质中的累计溶出率皆高达90%以上,与原料药相比溶出度得到显著提高;30 d加速稳定性实验结果显示,RES-AG SD溶出度与0月相比未发生明显改变,表明其能够保持一定的稳定性。结论 所制备的RES-AG SD能显著改善RES的溶出度,为RES的有效递送提供了新的制剂类型;AG作为一种新型药用功能性固体分散体载体,具有一定的实际应用价值。
Abstract
OBJECTIVE To study the application of arabinogalactan (AG) as a new type of polysaccharide carrier in solid dispersion formulations, select insoluble resveratrol (RES) as the model drug to prepare resveratrol-arabinogalactan solid dispersion (RES-AG SD) and evaluate it. METHODS RES-AG SD was prepared by solvent method with AG as carrier. Its microstructure was characterized and analyzed by differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The dissolution of API and RES-AG SD in pH 1.2 hydrochloric acid solution and pH 6.8 phosphate buffer solution was studied by slurry method, and their preliminary stability was evaluated. RESULTS SEM observation showed that RES-AG SD was in the shape of fine irregular particles, and the morphology of RES and AG was not seen. The results of DSC, XRD and FTIR showed that the crystal form of RES was destroyed and the diffraction peak of RES was almost disappeared. The drug was dispersed in AG in amorphous form, and there was a certain interaction between drug and carrier. In vitro dissolution experiments showed that the cumulative dissolution rate of RES in the two dissolution media was more than 90% at 2 h, and the dissolution rate was significantly improved compared with that of API. The results of 30 d accelerated stability test showed that the dissolution rate of RES-AG SD did not change significantly compared with that in 0 month, indicating that RES-AG SD could maintain a certain stability. CONCLUSION The prepared RES-AG SD can significantly improve the dissolution of RES, which provides a new route for the effective delivery of RES. As a new carrier of functional solid dispersion, AG has a certain practical application value.
关键词
阿拉伯半乳糖 /
白藜芦醇 /
固体分散体 /
体外溶出
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Key words
arabinogalactan /
resveratrol /
solid dispersion /
in vitro dissolution
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中图分类号：
R944
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参考文献
[1] LI X K, LI H Y, LI S, et al. Advances in study on resveratrol [J]. Chin Tradit Herb Drugs(中草药), 2016,47(14): 2568-2578.
[2] SIEMANN E, CREASY L L. Concentration of the phytoalexin resveratrol in wine [J]. Am J Enol Vitic, 1992, 43(1): 49-52.
[3] MATHIEU L, COSTA A L, BACHELIER C L, et al. Resveratrol attenuates oxidative stress in mitochondrial complex I deficiency: involvement of SIRT3 [J]. Free Radic Biol Med, 2016, 96:190-198.
[4] HWANG D, LIM Y H. Resveratrol antibacterial activity against Escherichia coli is mediated by Z-ring formation inhibition via suppression of FtsZ expression [J]. Sci Rep, 2015, 5(1): 10029-10045.
[5] DONG Q, WU Z, LI X, et al. Resveratrol ameliorates cardiac dysfunction induced by pressure overload in rats via structural protection and modulation of Ca2+ cycling proteins [J]. J Transl Med, 2014, 12(1): 323-334.
[6] HAO J F. Study on the resveratrol nanosuspensions for improvement of bioavailability and based on in situ gel for intranasal administration [D]. Jinan: Shandong University(山东大学), 2015.
[7] GUO Y F, LIN S X, LIU H Y, et al. Ultrasonic-assisted degradation of larch arabinogalactan and its antioxidant activity [J]. Forest By-Product and Speciality in China(中国林副特产), 2018,(1):4,8-11.
[8] TANG S, WANG T, HUANG C, et al. Sulfated modification of arabinogalactans from Larix principis-rupprechtii and their antitumor activities [J]. Carbohydr Polym, 2019, 215:207-212.
[9] Larch arabinogalactan [J]. Altern Med Rev, 2000, 5(5): 463-466.
[10] TANG S, JIANG M, HUANG C, et al. Characterization of arabinogalactans from Larix principis-rupprechtii and their effects on NO product ion by macrophages [J]. Carbohydr Polym, 2018, 200:408-415.
[11] MATTHIAS K, MAXIMILIAN J, ALICE V, et al. Total synthesis of a partial structure from arabinogalactan and its application for allergy-prevention [J]. Chemistry (Weinheim an der Bergstrasse, Germany), 2020, 27(3):928-933.
[12] TSVETELINA V, KALINA T-Y, RALITSA G, et al. Lactobacilli supplemented with larch arabinogalactan and colostrum stimulates an immune response towards peripheral NK activation and gut tolerance [J]. Nutrients, 2020, 12(6):1706-1716.
[13] QIHONG, ZHANG, LUBOV, et al. Preparation, physicochemical and pharmacological study of curcumin solid dispersion with an arabinogalactan complexation agent [J]. Int J Biol Macromol, 2019, 128:158-166.
[14] WANG S H, WANG R, SUN X D, et al. Application progress of solid dispersion and its technology in pharmaceutical preparations [J]. Guid J Tradit Chin Med Pharm(中医药导报), 2014, 20(10): 54-56.
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脚注
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基金
国家自然科学基金项目资助(81803756);江苏省“六个一工程”项目资助(LGY2019081);江苏省中医药研究院自主科研项目资助(BM2018024-2019014);江苏省重点学科组分中药工程学项目资助(ZDXK003)
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