Soluble thiabendazolium salts with anthelminthic properties

Area of Science:

• Pharmaceutical Science
• Drug Delivery
• Solid-State Chemistry

Background:

• Thiabendazole is an oral anthelmintic drug with low aqueous solubility, limiting its dissolution and absorption.
• Current chewable tablet formulations use excipients like sodium saccharinate, but solubility remains a challenge.
• Improving thiabendazole's solubility and palatability is crucial for effective oral drug delivery.

Purpose of the Study:

• To reformulate thiabendazole to enhance its aqueous solubility and palatability.
• To explore salt formation using various hydrogen donors (acids) to improve drug properties.
• To investigate the structural and physicochemical characteristics of novel thiabendazole salts.

Main Methods:

• Utilized solvothermal synthesis, neat grinding, and liquid-assisted grinding to form thiabendazole salts.
• Employed powder X-ray diffraction (PXRD) and single-crystal X-ray diffraction to confirm product formation and solve crystal structures.
• Characterized the salts using vibrational spectroscopy and thermoanalytical methods.

Main Results:

• Successfully synthesized thiabendazole salts with saccharin, fumaric acid, maleic acid, and oxalic acid.
• Achieved a 60-fold increase in aqueous solubility with the maleic acid salt, with modest improvements for saccharin and oxalic acid salts.
• Demonstrated significant tunability of solubility and intrinsic palatability through salt formation.

Conclusions:

• Salt formation is a viable strategy to enhance thiabendazole's aqueous solubility and palatability.
• The maleic acid co-former offers a promising route for developing improved oral and chewable thiabendazole formulations.
• These findings provide a foundation for new drug delivery strategies for helminthic infections.