Characterization and In vivo Evaluation of Polymorphic Valnemulin Hydrogen Fumarate

In the present study, a valnemulin hydrogen fumarate prodrug was characterized, its stability was compared with valnemulin hydrochloride, and the efficacy was evaluated in controlling pneumonia among mice experimentally infected with Actinobacillus pleuropneumoniae.

Optical microscopy, X-ray powder diffraction, infrared spectroscopy, and hydrogen nuclear magnetic resonance spectroscopy were used to study the physical and chemical properties of the prodrug. The thermal stability was investigated in comparison with valnemulin hydrochloride to improve the preparation process of valnemulin hydrogen fumarate soluble powder and maximize its drug effect. Additionally, the efficacy of valnemulin hydrogen fumarate was evaluated in a challenge-treatment trial in mice using an Actinobacillus pleuropneumoniae infection test in vivo.

Valnemulin hydrogen fumarate had high crystallinity. After light irradiation for 20 days, valnemulin hydrogen fumarate did not degrade, whereas valnemulin hydrochloride did. These results showed that the valnemulin hydrogen fumarate was stable. At the same dose in drinking water, the valnemulin hydrogen fumarate was more effective than the reference drug of tiamulin fumarate in an Actinobacillus pleuropneumoniae challenge-treatment trial.

Valnemulin hydrogen fumarate shows excellent potential for application as a veterinary drug.