Institute of Nuclear Medicine and Allied Sciences, Defence Research and Development Organization, New Delhi, India.
Delhi Institute of Pharmaceutical Sciences and Research, New Delhi, India.
Curr Drug Deliv. 2021;18(8):1162-1173. doi: 10.2174/1567201818666210127093327.
Prussian Blue (PB) is available as conventional release dosage form "Radiogardase" with effective daily dose of 3-10 g (very high). The target site is the duodenum, where it inhibits the enterohepatic circulation of Cs & Tl ions, enhancing their fecal excretion.
To enhance efficacy, target release, reduce the dose and side effects, oral pH-dependent matrix formulation of PB based on in-situ gelation of sodium alginate along with calcium salts was formulated and evaluated.
Different combinations of matrix granules were formulated and optimized. The optimized one was compressed using Polyvinylpyrrolidone K30 (Pvp K30) in different batches and optimized. Langmuir adsorption isotherm was used to assess in-vitro binding efficacy of formulation to thallium using atomic absorption spectroscopy. The proof of concept i.e., drug release in the duodenum was studied through pharmacoscintigraphy using radiolabeled formulation in rabbits.
The optimized granules showed no drug release in an acidic medium for 2 h whereas complete empty of the basket in a basic medium within 30-60 minutes. The matrix tablet formulation with Pvp K30 (10% w/w) was optimized with desired hardness and optimum in-vitro release profile. The release data fitted to various linear kinetic models, Hixson-Crowell r2 (0.9906) best fit, confirmed the erosion-based release mechanism. The maximum binding capacity (MBC) was found significantly higher (89.60 mg Tl/g formulation) than that of PB API (65.90 mg Tl /g PB API). Pharmacoscintigraphic images confirmed intact formulation in the stomach up to 2h and burst release in intestine thereafter.
The results exemplify oral pH-dependent PB matrix formulation which achieved desirable target release at the duodenum and in-vitro binding efficacy towards Tl ion was appreciable.
普鲁士蓝（PB）有常规释放剂型“Radiogardase”，有效日剂量为 3-10 克（非常高）。作用部位是十二指肠，在那里它抑制 Cs 和 Tl 离子的肠肝循环，增加它们的粪便排泄。
为了提高疗效、靶向释放、降低剂量和副作用，我们基于海藻酸钠原位凝胶化和钙盐，制备并评价了一种口服 pH 依赖性 PB 基质制剂。
我们制备并优化了不同组合的基质颗粒。优化后的颗粒用不同批次的聚乙烯吡咯烷酮 K30（Pvp K30）进行压缩并进行优化。使用原子吸收光谱法，通过 Langmuir 吸附等温线评估制剂对铊的体外结合效果。通过放射性标记制剂在兔体内进行药物代谢动力学研究，验证了概念验证，即药物在十二指肠的释放。
优化后的颗粒在酸性介质中 2 小时内没有药物释放，而在碱性介质中 30-60 分钟内完全排空篮。含有 10% w/w Pvp K30 的基质片剂制剂具有所需的硬度和最佳的体外释放特性。释放数据符合各种线性动力学模型，Hixson-Crowell r2（0.9906）拟合度最好，证实了基于侵蚀的释放机制。最大结合容量（MBC）显著高于 PB API（65.90 mg Tl/g PB API），达到 89.60 mg Tl/g 制剂。药物代谢动力学图像证实，在胃中完整的制剂可维持 2 小时，然后在肠道中迅速释放。
结果表明，口服 pH 依赖性 PB 基质制剂可在十二指肠实现理想的靶向释放，并且对 Tl 离子的体外结合效果令人满意。
