Prussian Blue Tablets for Cesium Decorporation: pH-Dependent Performance Under Normogastric and Hypochlorhydric...

Background/Objectives: Prussian blue (PB) is the agent of choice for internal cesium (Cs) decorporation, yet its performance is critically dependent on gastrointestinal (GI) pH and formulation attributes. Hypochlorhydria, common in patients treated with proton pump inhibitors, may alter the stagewise distribution of Cs binding during GI transit. This study aimed to compare the performance of different PB formulations in sequential in vitro models simulating normogastria and hypochlorhydria: normogastric regimen (NG) and hypochlorhydric regimen (HC). Methods: A static, enzyme-free sequential model was applied using compendial simulated fluids (SGFs pH 1.2 or acetate pH 4.0, SIF pH 6.8, and phosphate buffer pH 7.2). The formulations tested included PB active pharmaceutical ingredient (API) (bulk), compression blend, PB tablets 500 mg (PB tablets), and Radiogardase^®. For each stage, cesium bound (qs, mg/g PB), fractional contributions (fs), and total capture (qtotal) were quantified. Additional analyses included sensitivity to initial Cs concentration (C₀) and desorption in mineralized water. Results: Overall performance was primarily determined by formulation (p < 0.0001), with a significant formulation × regimen interaction. The compression blend and PB tablets exhibited the highest decorporation capacity, PB-API showed intermediate performance, and Radiogardase^® was clearly lower. Under HC, capture was concentrated in the gastric stage (44-47%), whereas in NG, it shifted toward intestinal stages. Desorption in the mineralized water was statistically significant but negligible compared with total capture, supporting the stability of cesium sequestration. Conclusions: Formulation and gastric acidity regimens not only determine the total cesium capture but also redistribute it across the GI tract. PB tablets represent an effective and accessible alternative to Radiogardase^®, maintaining robust decorporation capacity under clinically relevant pH conditions.