Albendazole solid dispersions prepared using PEG6000 and Poloxamer188: formulation, characterization andin vivoevaluation
Albendazole solid dispersions prepared using PEG6000 and Poloxamer188: formulation, characterization andin vivoevaluation
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DOI：
10.1080/10837450.2020.1783553
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发表时间：
2020-07-03
影响因子：
3.4
通讯作者：
Li, Yan-Hua
中科院分区：
文献类型：
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作者：
Dong, Chun-Liu;Zheng, Si-Di;Li, Yan-Hua
本研究旨在优化阿苯达唑固体分散体(SD)的制备工艺，提高其在犬体内的溶出度和口服生物利用度。ABZ-SD制剂由ABZ与聚乙二醇6000(PEG6000)、泊洛沙姆188(P188)聚合物按不同重量比或PEG6000与P188的组合通过熔融方法制备。采用扫描电子显微镜(SEM)、粉末X-射线衍射仪(PXRD)、傅立叶变换红外光谱(FTIR)、体外溶出度和分子对接等方法对最佳处方进行了表征。在Beagle犬体内进行了体内药代动力学研究。结果成功地制备了以PEG6000和P188(1：2)为基质的ABZ固体分散体。与市售片剂相比，ABZ-SD制剂能显著提高ABZ的表观溶出度和溶出度。此外，ABZ-SD的水溶性能主要是通过氢键缔合作用得到改善。此外，在口服15 mg/kg ABZ时，与市售ABZ片剂相比，SDS的Cmax和曲线下面积(AUC)更高。聚乙二醇6000和聚乙二醇188制备阿维菌素十二烷基硫酸酯是提高阿维菌素口服生物利用度的一种有前途的策略。
This study aimed to optimize the preparation process of albendazole (ABZ) solid dispersion (SD) and enhance its dissolution rate and oral bioavailability in dogs. The ABZ-SD formulations were prepared by a fusion method with ABZ and polyethylene glycol 6000 (PEG 6000), poloxamer 188 (P 188) polymers at various weight ratios or the combination of PEG 6000&P 188. The characterizations of the optimal formulations were performed by scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR),in vitrodissolution test and molecular docking. Thein vivopharmacokinetic study was conducted in beagle dogs. As a result, ABZ solid dispersion based on PEG 6000&P 188 (1:2) was successfully prepared. The ABZ-SD formulation could significantly improve the apparent solubility and dissolution rate of ABZ compared with commercial tablets. Furthermore, the water solubility of ABZ-SD was improved mainly based on hydrogen bond association. Besides, at an oral dosage of 15 mg/kg ABZ, the SDs had higher Cmax values and areas under the curve (AUCs) compared to those of commercial ABZ tablets. Preparation of ABZ-loaded SDs by PEG 6000&P 188 is a promising strategy to improve the oral bioavailability of ABZ.