pH-dependent Release Matrix Oral Formulation of Prussian Blue to Improve its Efficacy as an Internal Decorporation Agent

Abstract

Background: 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.

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Alginate(s); Atomic absorption spectroscopy; Decorporation; Prussian blue.; Targeted drug delivery; Thallium; pH-dependent release.