Mechanochemical Synthesis of A Novel Eutectic of the Antimicrobial Nitazoxanide with Improved Dissolution Performance

Background: Nitazoxanide (NTZ) is a broad spectrum antimicrobial agent with poor aqueous solubility and low bioavailability. Thus, the generation of new solid forms of NTZ is relevant to improve its unfavorable properties. The present study deals with the application of mechanochemistry for the prep...

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Autores principales:	Octavio E. Fandiño, Flavia P Bruno, Gustavo A. Monti, Norma R. Sperandeo
Formato:	article
Lenguaje:	EN
Publicado:	Tabriz University of Medical Sciences 2021
Materias:	differential scanning calorimetry dissolution efficiency liquid-assisted grinding powder dissolution saccharine x-ray powder diffraction Pharmacy and materia medica RS1-441
Acceso en línea:	https://doaj.org/article/6c47f72ff9d34083b049dc5cd96f36b4
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spelling	oai:doaj.org-article:6c47f72ff9d34083b049dc5cd96f36b42021-11-29T05:54:20ZMechanochemical Synthesis of A Novel Eutectic of the Antimicrobial Nitazoxanide with Improved Dissolution Performance2383-288610.34172/PS.2021.10https://doaj.org/article/6c47f72ff9d34083b049dc5cd96f36b42021-12-01T00:00:00Zhttps://ps.tbzmed.ac.ir/PDF/ps-27-585.pdfhttps://doaj.org/toc/2383-2886Background: Nitazoxanide (NTZ) is a broad spectrum antimicrobial agent with poor aqueous solubility and low bioavailability. Thus, the generation of new solid forms of NTZ is relevant to improve its unfavorable properties. The present study deals with the application of mechanochemistry 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) and characterized using differential scanning calorimetry (DSC), hot stage microscopy (HSM), X-ray Powder Diffraction (XRPD), 13C Solid-state Nuclear Magnetic Resonance (SSNMR) andDiffuse Reflectance Infrared Fourier Transform (DRIFT) spectroscopy. Powder dissolution (PD)profiles were obtained with USP apparatus 2 in buffer phosphate pH 6.5 with 0.25% TweenÒ 80- 0.25% triethanolamine and in 0.25% sodium lauryl sulfate, at 37 ºC ± 0.5 ºC and 75 rpm. Drug release was characterized in terms of dissolution efficiency (DE). Results: XRPD, SSNMR and DRIFT indicated that NTZ and SAC did not cocrystallize but DSCand HSM revealed that they formed a binary eutectic mixture which melted near 176 °C, a melting temperature lower than those of NTZ and SAC. PD data indicated that the 1:1 NTZSACsample obtained by LAG exhibited a slightly higher DE than pure NTZ in the two assayed media. Conclusion: NTZ and SAC formed a eutectic, the first reported for this drug, which improved its dissolution rate and opened the pathway for studies searching for new eutectics with better biopharmaceutical attributes than NTZ and the NTZ-SAC eutectic reported herein.Octavio E. FandiñoFlavia P BrunoGustavo A. MontiNorma R. SperandeoTabriz University of Medical Sciencesarticledifferential scanning calorimetrydissolution efficiencyliquid-assisted grindingpowder dissolutionsaccharinex-ray powder diffractionPharmacy and materia medicaRS1-441ENPharmaceutical Sciences, Vol 27, Iss 4, Pp 585-592 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	differential scanning calorimetry dissolution efficiency liquid-assisted grinding powder dissolution saccharine x-ray powder diffraction Pharmacy and materia medica RS1-441
spellingShingle	differential scanning calorimetry dissolution efficiency liquid-assisted grinding powder dissolution saccharine x-ray powder diffraction Pharmacy and materia medica RS1-441 Octavio E. Fandiño Flavia P Bruno Gustavo A. Monti Norma R. Sperandeo Mechanochemical Synthesis of A Novel Eutectic of the Antimicrobial Nitazoxanide with Improved Dissolution Performance
description	Background: Nitazoxanide (NTZ) is a broad spectrum antimicrobial agent with poor aqueous solubility and low bioavailability. Thus, the generation of new solid forms of NTZ is relevant to improve its unfavorable properties. The present study deals with the application of mechanochemistry 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) and characterized using differential scanning calorimetry (DSC), hot stage microscopy (HSM), X-ray Powder Diffraction (XRPD), 13C Solid-state Nuclear Magnetic Resonance (SSNMR) andDiffuse Reflectance Infrared Fourier Transform (DRIFT) spectroscopy. Powder dissolution (PD)profiles were obtained with USP apparatus 2 in buffer phosphate pH 6.5 with 0.25% TweenÒ 80- 0.25% triethanolamine and in 0.25% sodium lauryl sulfate, at 37 ºC ± 0.5 ºC and 75 rpm. Drug release was characterized in terms of dissolution efficiency (DE). Results: XRPD, SSNMR and DRIFT indicated that NTZ and SAC did not cocrystallize but DSCand HSM revealed that they formed a binary eutectic mixture which melted near 176 °C, a melting temperature lower than those of NTZ and SAC. PD data indicated that the 1:1 NTZSACsample obtained by LAG exhibited a slightly higher DE than pure NTZ in the two assayed media. Conclusion: NTZ and SAC formed a eutectic, the first reported for this drug, which improved its dissolution rate and opened the pathway for studies searching for new eutectics with better biopharmaceutical attributes than NTZ and the NTZ-SAC eutectic reported herein.
format	article
author	Octavio E. Fandiño Flavia P Bruno Gustavo A. Monti Norma R. Sperandeo
author_facet	Octavio E. Fandiño Flavia P Bruno Gustavo A. Monti Norma R. Sperandeo
author_sort	Octavio E. Fandiño
title	Mechanochemical Synthesis of A Novel Eutectic of the Antimicrobial Nitazoxanide with Improved Dissolution Performance
title_short	Mechanochemical Synthesis of A Novel Eutectic of the Antimicrobial Nitazoxanide with Improved Dissolution Performance
title_full	Mechanochemical Synthesis of A Novel Eutectic of the Antimicrobial Nitazoxanide with Improved Dissolution Performance
title_fullStr	Mechanochemical Synthesis of A Novel Eutectic of the Antimicrobial Nitazoxanide with Improved Dissolution Performance
title_full_unstemmed	Mechanochemical Synthesis of A Novel Eutectic of the Antimicrobial Nitazoxanide with Improved Dissolution Performance
title_sort	mechanochemical synthesis of a novel eutectic of the antimicrobial nitazoxanide with improved dissolution performance
publisher	Tabriz University of Medical Sciences
publishDate	2021
url	https://doaj.org/article/6c47f72ff9d34083b049dc5cd96f36b4
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Mechanochemical Synthesis of A Novel Eutectic of the Antimicrobial Nitazoxanide with Improved Dissolution Performance

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