Oral formulation of Prussian blue with improved efficacy for prophylactic use against thallium

Abstract

Objective

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).

Methods

The capsule formulation was optimized with desired in vitro 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 in vivo study was performed in rats to determine the removal efficacy of optimized formulation (FF4) for Tl.

Results

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 (C_max) and Area under Curve (AUC) as compared to the control.

Conclusion

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.

Graphical Abstract

Keywords:

• Prussian blue
• decorporation
• cesium
• thallium
• pH modifying agent
• magnesium hydroxide

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The authors are thankful to the Defence Research and Development Organization (DRDO)-Institute of Nuclear Medicine and Allied Sciences (INMAS), Ministry of Defence, New Delhi for financial assistance to carry out these studies under the task project INM/01/S&T/18-19.