阿苯达唑(ABZ)是一种高效但水溶性差的抗寄生虫药物,已知可形成盐(ABZ-FMA,ABZ-DTA,和ABZ-HCl)与富马酸(FMA),D-酒石酸(DTA),和盐酸(HCl)。这项研究利用了一系列分析技术,包括傅里叶变换红外光谱(FT-IR),核磁共振氢谱(1HNMR),粉末X射线衍射(PXRD),动态蒸汽吸附(DVS),热重分析(TGA),差示扫描量热法(DSC),和扫描电子显微镜(SEM),以验证和表征这些药物盐的固态性质。该研究还评估了这些盐在不同pH条件下与活性药物成分(API)相比的溶解度和固有溶出速率(IDR),并进行了稳定性研究。此外,评估了ABZ盐的体内药代动力学性能。这项研究的结果表明,ABZ的新固体形式主要与氨基酸酯和苯并咪唑基团有关,形成分子间相互作用。所有三种ABZ盐均显着提高了ABZ的溶解度和溶解速率,ABZ-HCl证明了最佳性能。重要的是,药物盐在暴露于不利条件时表现出强大的物理稳定性,包括强光照射(4500±500勒克斯),高湿度(92.5±5%相对湿度),高温(50±2°C),和加速试验条件(40°C/75±5%相对湿度)。最后,体内药代动力学分析表明,与ABZ相比,ABZ盐导致AUC(0-24)和Cmax显著增加.在水性溶剂中溶解度的这种提高表明ABZ盐表现出可以增强口服生物利用度和药代动力学的特征。这些发现为开发更有效和创新的药物制剂提供了潜在的解决方案。
Albendazole (ABZ) is a highly effective yet poorly water-soluble antiparasitic drug known to form salts (ABZ-FMA, ABZ-DTA, and ABZ-HCl) with fumaric acid (FMA), D-tartaric acid (DTA), and hydrochloric acid (HCl). This research utilized a range of analytical techniques, including Fourier transform infrared spectroscopy (FT-IR), nuclear magnetic resonance hydrogen spectroscopy (1H NMR), powder X-ray diffraction (PXRD), dynamic vapor sorption (DVS), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM), to validate and characterize the solid-state properties of these drug salts. This study also assessed the solubility and intrinsic dissolution rate (IDR) of these salts under different pH conditions compared to the active pharmaceutical ingredient (API) and conducted stability studies. Moreover, the in vivo pharmacokinetic performance of ABZ salt was evaluated. The results of this study reveal that the new solid form of ABZ is primarily associated with amino acid esters and benzimidazole groups, forming intermolecular interactions. All three ABZ salts significantly improved the solubility and dissolution rate of ABZ, with ABZ-HCl demonstrating the optimal performance. Importantly, the drug salt exhibited robust physical stability when exposed to adverse conditions, including strong light irradiation (4500 ± 500 lux), high humidity (92.5 ± 5% relative humidity), elevated temperatures (50 ± 2 °C), and accelerated test conditions (40 °C/75 ± 5% relative humidity). Lastly, the in vivo pharmacokinetic analysis demonstrated that ABZ salt led to a substantial increase in AUC(0-24) and Cmax compared to ABZ. This elevation in solubility in aqueous solvents signifies that ABZ salt exhibits characteristics that can enhance oral bioavailability and pharmacokinetics. These findings provide potential solutions for the development of more effective and innovative drug formulations.