Sandal Nidhi, Kumar Vivek, Sharma Pooja, Yadav Mahendra
Defence Research and Development Organization, Institute of Nuclear Medicine and Allied Sciences, New Delhi, India.
Drug Dev Ind Pharm. 2023 Feb;49(2):149-158. doi: 10.1080/03639045.2023.2189958. Epub 2023 Mar 22.
The present study is aimed to enhance the efficacy of Insoluble Prussian blue (PB) in the stomach. PB formulation was developed comprising of PB in combination with pH modifying agents particularly magnesium hydroxide, calcium carbonate, sodium carbonate, and sodium bicarbonate. pH profile and the binding efficacy of the final formulation was evaluated in simulated gastric fluid (SGF).
The capsule formulation was optimized with desired characteristics. The final formulations (FF1-FF4) were evaluated for drug release, pH profile, and binding efficacy for thallium (Tl). The stability studies were performed in terms of drug assay, Fourier-transformed infrared (FTIR) spectroscopy and Thermo-gravimetric analysis (TGA). The study was performed in rats to determine the removal efficacy of optimized formulation (FF4) for Tl.
The PB formulation consisting of optimized PB granules and pH modifying agents showed a significant increase in the binding efficacy for Tl in SGF at an equilibrium time of 24 h. The Maximum Binding Capacity (MBC) of FF1-FF4 was found to be higher than commercially available Radiogardase-Cs capsules and PB granules alone in SGF. The blood Tl level in rats treated with FF4 showed three-fold decreases in the level of Tl in the blood () and Area under Curve (AUC) as compared to the control.
The results revealed that the developed oral PB formulation has a significantly higher efficiency of binding Tl at the acidic pH of the stomach thereby reducing its absorption into the systemic circulation. Thus, the optimized formulation of PB with pH-modifying agents is a better drug for prophylactic use in thallium ingestion.
本研究旨在提高胃内不溶性普鲁士蓝（PB）的疗效。开发了一种PB制剂，其由PB与pH调节剂（特别是氢氧化镁、碳酸钙、碳酸钠和碳酸氢钠）组合而成。在模拟胃液（SGF）中评估了最终制剂的pH曲线和结合效果。
对胶囊制剂进行优化以具备所需特性。对最终制剂（FF1 - FF4）进行药物释放、pH曲线和铊（Tl）结合效果的评估。通过药物含量测定、傅里叶变换红外（FTIR）光谱和热重分析（TGA）进行稳定性研究。在大鼠中进行研究以确定优化制剂（FF4）对Tl的清除效果。
由优化的PB颗粒和pH调节剂组成的PB制剂在24小时平衡时间时，在SGF中对Tl的结合效果显著增加。在SGF中，发现FF1 - FF4的最大结合容量（MBC）高于市售的Radiogardase - Cs胶囊和单独的PB颗粒。与对照组相比，用FF4治疗的大鼠血液中的Tl水平和曲线下面积（AUC）显示血液中Tl水平降低了三倍。
结果表明，所开发的口服PB制剂在胃的酸性pH下结合Tl的效率显著更高，从而减少其吸收进入体循环。因此，优化的含pH调节剂的PB制剂是铊摄入预防性使用的更好药物。
