Su Dehai, Bai Mingyang, Wei Chaoqun, Long Xiangyang, Liu Xuezhen, Shen Xiangguang, Ding Huanzhong
Guangdong Key Laboratory for Veterinary Drug Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University (SCAU), Guangzhou, China.
Front Vet Sci. 2024 Dec 20;11:1522856. doi: 10.3389/fvets.2024.1522856. eCollection 2024.
Albendazole (ABZ), classified as a class II basic drug under the Biopharmaceutics Classification System (BCS), is widely recognized for its therapeutic efficacy in treating and preventing trichuriasis. However, despite its clinical relevance, ABZ's oral administration presents challenges due to its poor solubility and pH sensitivity, which diminish its therapeutic effectiveness. Additionally, high dosing regimens of ABZ pose risks of developmental toxicity in animal models. This study developed a pH-sensitive solid dispersion of albendazole (ABZ-pHs-SD) using Glyceryl Monostearate (GM) in conjunction with Hypromellose Acetate Succinate (HPMC-AS). Characterization via Scanning Electron Microscopy (SEM), Powder X-ray Diffraction (PXRD), Differential Scanning Calorimetry (DSC), and Fourier Transform Infrared Spectroscopy (FT-IR) confirmed the high dispersion of ABZ in a crystalline state within the carrier. Furthermore, we compared the dissolution profile, pharmacokinetics, and intestinal drug concentration of ABZ-pHs-SD with commercially available formulations. Our findings demonstrated that ABZ-pHs-SD exhibited an excellent dissolution profile, significantly increasing the solubility of ABZ in water by 3.15 times. The formulation effectively prevented drug release in acidic environments while maintaining a slow release in weakly alkaline conditions. Additionally, compared to commercial formulations, ABZ-pHs-SD showed significantly lower C (4.70 ± 1.16 vs. 6.83 ± 0.66 μg/mL) and higher T (5.5 ± 0.93 vs. 3.75 ± 0.71 h) , achieving elevated drug concentration levels in the cecal and colonic environments ( < 0.01) without significantly decreasing bioavailability. Overall, our research findings indicate that ABZ-pHs-SD serves as a promising drug delivery strategy for the poorly soluble and pH-sensitive ABZ. Particularly, the simple preparation of solid dispersion demonstrates strong industrial feasibility.
阿苯达唑（ABZ）在生物药剂学分类系统（BCS）中被归类为II类碱性药物，其在治疗和预防鞭虫病方面的治疗效果广为人知。然而，尽管其具有临床相关性，但由于其溶解度差和pH敏感性，阿苯达唑的口服给药存在挑战，这降低了其治疗效果。此外，高剂量的阿苯达唑给药方案在动物模型中存在发育毒性风险。本研究使用单硬脂酸甘油酯（GM）与醋酸羟丙甲纤维素琥珀酸酯（HPMC-AS）联合开发了一种pH敏感的阿苯达唑固体分散体（ABZ-pHs-SD）。通过扫描电子显微镜（SEM）、粉末X射线衍射（PXRD）、差示扫描量热法（DSC）和傅里叶变换红外光谱（FT-IR）进行表征，证实了阿苯达唑在载体中以结晶状态高度分散。此外，我们比较了ABZ-pHs-SD与市售制剂的溶出曲线、药代动力学和肠道药物浓度。我们的研究结果表明，ABZ-pHs-SD表现出优异的溶出曲线，使阿苯达唑在水中的溶解度显著提高了3.15倍。该制剂有效地防止了药物在酸性环境中的释放，同时在弱碱性条件下保持缓慢释放。此外，与市售制剂相比，ABZ-pHs-SD的C显著更低（4.70±1.16 vs. 6.83±0.66μg/mL），T显著更高（5.5±0.93 vs. 3.75±0.71 h），在盲肠和结肠环境中实现了更高的药物浓度水平（<0.01），而生物利用度没有显著降低。总体而言，我们的研究结果表明，ABZ-pHs-SD是一种针对难溶性和pH敏感的阿苯达唑很有前景的药物递送策略。特别是，固体分散体的简单制备显示出很强的工业可行性。
