Mechanochemical synthesis of a novel eutectic of the antimicrobial nitazoxanide with improved dissolution performance

FANDIÑO, OCTAVIO E.; BRUNO, FLAVIA P; MONTI, GUSTAVO A.; SPERANDEO, NORMA R.

PHARMACEUTICAL SCIENCES

Tabriz University of Medical Sciences

Año: 2021

1735-403X

ackground: Nitazoxanide (NTZ) is a broad spectrum antimicrobial agent with poor aqueoussolubility and low bioavailability. Thus, the generation of new solid forms of NTZ is relevant toimprove its unfavorable properties. The present study deals with the application ofmechanochemistry for the preparation of alternate solid forms of NTZ, using saccharine (SAC)as coformer.Methods: NTZ-SAC mixtures were prepared by neat and liquid-assisted grinding (LAG) andcharacterized using differential scanning calorimetry (DSC), hot stage microscopy (HSM), X-rayPowder Diffraction (XRPD),13C Solid-state Nuclear Magnetic Resonance (SSNMR) and DiffuseReflectance Infrared Fourier Transform (DRIFT) spectroscopy. Powder dissolution (PD) profileswere obtained with USP apparatus 2 in buffer phosphate pH 6.5 with 0.25% Tween 80 - 0.25%triethanolamine and in 0.25% sodium lauryl sulfate, at 37 ºC  0.5 ºC and 75 rpm. Drug releasewas characterized in terms of dissolution efficiency (DE).Results: XR