Pharmaceutics, AISSMS College of Pharmacy, Pune, India.
Drug Dev Ind Pharm. 2021 Mar;47(3):367-376. doi: 10.1080/03639045.2021.1879830. Epub 2021 Mar 15.
Improving solubility and bioavailability of albendazole (ALB).
ALB is a broad-spectrum anthelminthic BCS class II drug with aqueous solubility of solubility of 4.1 mg/l at 25 °C and oral bioavailability of <5%.
ALB nanosuspensions (NSs) were prepared by evaporative antisolvent precipitation using tocopherol polyethylene glycol succinate (TPGS) and polyvinyl pyrrolidone (PVP) as stabilizers and characterized for particle size, polydispersity index, and zeta potential. 3 factorial design was used to investigate effect of stabilizer concentration and speed of stirring on particle size. Concentration of TPGS was varied from 0.03 to 0.05% w/v and PVP K-30 was constant at 0.04% w/v. Stirring speed range was 1000-3000 rpm. Optimized NS was loaded on Espheres and coated with Eudragit S10& L100 and studied for friability, surface morphology and release kinetics.
Factorial experiments revealed pronounced effect of TPGS on particle size. Optimized batch had particle size of 251 ± 7.2 nm and zeta potential -16.2 ± 2.68 mV. Saturation solubility showed increase of 16-fold in water whereas in phosphate buffer increase was fourfold. ALB-NS secondary coated Espheres released 94.3% drug in 10 h whereas ALB-MS (microsuspension) coated Espheres showed 58% release. A 1.3-fold increase in AUC was evident. Permeation from ALB-NS coated Espheres was 32% in 60 min while for ALB-MS coated Espheres it was 20%. Permeation increase occurred due to presence of TPGS which acts as a permeation enhancer.
提高阿苯达唑（ALB）的溶解度和生物利用度。
ALB 是一种广谱驱虫药，属于 BCS 分类 II 药物，在 25°C 时的水溶解度为 4.1mg/l，口服生物利用度<5%。
采用醇相蒸发抗溶剂沉淀法制备 ALB 纳米混悬剂（NS），以生育酚聚乙二醇琥珀酸酯（TPGS）和聚乙烯吡咯烷酮（PVP）为稳定剂，并对其粒径、多分散指数和zeta 电位进行了表征。采用 3 因素设计考察稳定剂浓度和搅拌速度对粒径的影响。TPGS 浓度范围为 0.03-0.05%（w/v），PVP K-30 浓度固定在 0.04%（w/v）。搅拌速度范围为 1000-3000rpm。优化后的 NS 载入 Espheres 并用 Eudragit S10&L100 包衣，考察其脆碎度、表面形态和释放动力学。
实验结果表明 TPGS 对粒径有显著影响。优化后的批次粒径为 251±7.2nm，zeta 电位为-16.2±2.68mV。在水中的饱和溶解度增加了 16 倍，而在磷酸盐缓冲液中增加了 4 倍。ALB-NS 二次包衣的 Espheres 在 10 小时内释放了 94.3%的药物，而 ALB-MS（微悬浮液）包衣的 Espheres 释放了 58%的药物。AUC 增加了 1.3 倍。ALB-NS 包衣 Espheres 的渗透量在 60 分钟时为 32%，而 ALB-MS 包衣 Espheres 的渗透量为 20%。渗透增加是由于存在 TPGS，它作为一种渗透增强剂。
