Lan Sumin, Chen Kexi, Feng Liqiang, Sima Panle, Ji Xiaoyao, Wu Feihua, Lin Yining
School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, China.
Xizang Provincial Center for Disease Control and Prevention, Lasa, 850000, China.
AAPS PharmSciTech. 2025 Jan 8;26(1):22. doi: 10.1208/s12249-024-03015-1.
Albendazole serves as a broad-spectrum anthelmintic medication for treating hydatid cysts and neurocysticercosis. However, its therapeutic effectiveness is limited by poor solubility. Nanocrystals offer a promising technology to address this limitation by enhancing drug solubility. The objective of this study is to evaluate an effective stabilizer for creating an albendazole nanocrystal formulation to improve oral absorption. Among different surfactants and polymers examined, tea saponins were used as the stabilizer to develop a nanosuspension with the particle size of 180 nm through a wet grinding approach. The physical characteristics of the nanocrystals were assessed using SEM, DSC, and XRPD. The nanocrystals significantly enhanced solubility by 2.9-2602 fold in different media and showed significant enhancement in dissolution rate compared to albendazole crystals in both pH 1.0 and pH 6.8 medium. Everted gut sacs experiments demonstrated that the nanocrystals increased P by 3.60-fold in duodenum, 3.76-fold in jejunum, 3.71-fold in ileum, and 5.26-fold in colon, respectively. Furthermore, pharmacokinetic studies revealed that the nanocrystals significantly enhanced oral bioavailability, resulting in a 4.65-fold increase in plasma AUC value of albendazole sulfoxide (the primary active metabolite of albendazole) compared to the albendazole group. The present data indicates that tea saponins are potential natural stabilizers for preparing nanocrystals with enhanced oral bioavailability for insoluble drugs.
阿苯达唑是一种用于治疗包虫囊肿和神经囊尾蚴病的广谱驱虫药。然而，其治疗效果受到溶解度差的限制。纳米晶体提供了一种有前景的技术，可通过提高药物溶解度来解决这一限制。本研究的目的是评估一种有效的稳定剂，以制备阿苯达唑纳米晶体制剂，提高口服吸收。在所研究的不同表面活性剂和聚合物中，茶皂素被用作稳定剂，通过湿磨法制备了粒径为180nm的纳米混悬液。使用扫描电子显微镜（SEM）、差示扫描量热法（DSC）和X射线粉末衍射（XRPD）对纳米晶体的物理特性进行了评估。纳米晶体在不同介质中的溶解度显著提高了2.9至2602倍，并且在pH 1.0和pH 6.8介质中与阿苯达唑晶体相比，溶解速率显著提高。外翻肠囊实验表明，纳米晶体在十二指肠、空肠、回肠和结肠中的透过率分别提高了3.60倍、3.76倍、3.71倍和5.26倍。此外，药代动力学研究表明，纳米晶体显著提高了口服生物利用度，与阿苯达唑组相比，阿苯达唑亚砜（阿苯达唑的主要活性代谢产物）的血浆AUC值增加了4.65倍。目前的数据表明，茶皂素是制备具有提高口服生物利用度的难溶性药物纳米晶体的潜在天然稳定剂。
