Synthesis, Characterization, and Intrinsic Dissolution Studies of Drug–Drug Eutectic Solid Forms of Metformin Hydrochloride and Thiazide Diuretics

The mechanochemical synthesis of drug–drug solid forms containing metformin hydrochloride (MET·HCl) and thiazide diuretics hydrochlorothiazide (HTZ) or chlorothiazide (CTZ) is reported. Characterization of these new systems indicates formation of binary eutectic conglomerates, i.e., drug–drug eutect...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Guadalupe Coyote-Dotor, José C. Páez-Franco, Daniel Canseco-González, Alejandra Núñez-Pineda, Alejandro Dorazco-González, Inés Fuentes-Noriega, Alfredo R. Vilchis-Néstor, Joelis Rodríguez-Hernández, David Morales-Morales, Juan Manuel Germán-Acacio
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	drug–drug eutectic solid forms mechanochemical reactions intrinsic dissolution experiments Pharmacy and materia medica RS1-441
Acceso en línea:	https://doaj.org/article/3a70b6590cef4096b69afd6913f837f7
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:3a70b6590cef4096b69afd6913f837f7
record_format	dspace
spelling	oai:doaj.org-article:3a70b6590cef4096b69afd6913f837f72021-11-25T18:41:56ZSynthesis, Characterization, and Intrinsic Dissolution Studies of Drug–Drug Eutectic Solid Forms of Metformin Hydrochloride and Thiazide Diuretics10.3390/pharmaceutics131119261999-4923https://doaj.org/article/3a70b6590cef4096b69afd6913f837f72021-11-01T00:00:00Zhttps://www.mdpi.com/1999-4923/13/11/1926https://doaj.org/toc/1999-4923The mechanochemical synthesis of drug–drug solid forms containing metformin hydrochloride (MET·HCl) and thiazide diuretics hydrochlorothiazide (HTZ) or chlorothiazide (CTZ) is reported. Characterization of these new systems indicates formation of binary eutectic conglomerates, i.e., drug–drug eutectic solids (DDESs). Further analysis by construction of binary diagrams (DSC screening) exhibited the characteristic V-shaped form indicating formation of DDESs in both cases. These new DDESs were further characterized by different techniques, including thermal analysis (DSC), solid state NMR spectroscopy (SSNMR), powder X-ray diffraction (PXRD) and scanning electron microscopy–energy dispersive X-ray spectroscopy analysis (SEM–EDS). In addition, intrinsic dissolution rate experiments and solubility assays were performed. In the case of MET·HCl-HTZ (χ<sub>MET·HCl</sub> = 0.66), we observed a slight enhancement in the dissolution properties compared with pure HTZ (1.21-fold). The same analysis for the solid forms of MET·HCl-CTZ (χ<sub>MET·HCl</sub> = 0.33 and 0.5) showed an enhancement in the dissolved amount of CTZ accompanied by a slight improvement in solubility. From these dissolution profiles and saturation solubility studies and by comparing the thermodynamic parameters (ΔH<sub>fus</sub> and ΔS<sub>fus</sub>) of the pure drugs with these new solid forms, it can be observed that there was a limited modification in these properties, not modifying the free energy of the solution (ΔG) and thus not allowing an improvement in the dissolution and solubility properties of these solid forms.Guadalupe Coyote-DotorJosé C. Páez-FrancoDaniel Canseco-GonzálezAlejandra Núñez-PinedaAlejandro Dorazco-GonzálezInés Fuentes-NoriegaAlfredo R. Vilchis-NéstorJoelis Rodríguez-HernándezDavid Morales-MoralesJuan Manuel Germán-AcacioMDPI AGarticledrug–drug eutectic solid formsmechanochemical reactionsintrinsic dissolution experimentsPharmacy and materia medicaRS1-441ENPharmaceutics, Vol 13, Iss 1926, p 1926 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	drug–drug eutectic solid forms mechanochemical reactions intrinsic dissolution experiments Pharmacy and materia medica RS1-441
spellingShingle	drug–drug eutectic solid forms mechanochemical reactions intrinsic dissolution experiments Pharmacy and materia medica RS1-441 Guadalupe Coyote-Dotor José C. Páez-Franco Daniel Canseco-González Alejandra Núñez-Pineda Alejandro Dorazco-González Inés Fuentes-Noriega Alfredo R. Vilchis-Néstor Joelis Rodríguez-Hernández David Morales-Morales Juan Manuel Germán-Acacio Synthesis, Characterization, and Intrinsic Dissolution Studies of Drug–Drug Eutectic Solid Forms of Metformin Hydrochloride and Thiazide Diuretics
description	The mechanochemical synthesis of drug–drug solid forms containing metformin hydrochloride (MET·HCl) and thiazide diuretics hydrochlorothiazide (HTZ) or chlorothiazide (CTZ) is reported. Characterization of these new systems indicates formation of binary eutectic conglomerates, i.e., drug–drug eutectic solids (DDESs). Further analysis by construction of binary diagrams (DSC screening) exhibited the characteristic V-shaped form indicating formation of DDESs in both cases. These new DDESs were further characterized by different techniques, including thermal analysis (DSC), solid state NMR spectroscopy (SSNMR), powder X-ray diffraction (PXRD) and scanning electron microscopy–energy dispersive X-ray spectroscopy analysis (SEM–EDS). In addition, intrinsic dissolution rate experiments and solubility assays were performed. In the case of MET·HCl-HTZ (χ<sub>MET·HCl</sub> = 0.66), we observed a slight enhancement in the dissolution properties compared with pure HTZ (1.21-fold). The same analysis for the solid forms of MET·HCl-CTZ (χ<sub>MET·HCl</sub> = 0.33 and 0.5) showed an enhancement in the dissolved amount of CTZ accompanied by a slight improvement in solubility. From these dissolution profiles and saturation solubility studies and by comparing the thermodynamic parameters (ΔH<sub>fus</sub> and ΔS<sub>fus</sub>) of the pure drugs with these new solid forms, it can be observed that there was a limited modification in these properties, not modifying the free energy of the solution (ΔG) and thus not allowing an improvement in the dissolution and solubility properties of these solid forms.
format	article
author	Guadalupe Coyote-Dotor José C. Páez-Franco Daniel Canseco-González Alejandra Núñez-Pineda Alejandro Dorazco-González Inés Fuentes-Noriega Alfredo R. Vilchis-Néstor Joelis Rodríguez-Hernández David Morales-Morales Juan Manuel Germán-Acacio
author_facet	Guadalupe Coyote-Dotor José C. Páez-Franco Daniel Canseco-González Alejandra Núñez-Pineda Alejandro Dorazco-González Inés Fuentes-Noriega Alfredo R. Vilchis-Néstor Joelis Rodríguez-Hernández David Morales-Morales Juan Manuel Germán-Acacio
author_sort	Guadalupe Coyote-Dotor
title	Synthesis, Characterization, and Intrinsic Dissolution Studies of Drug–Drug Eutectic Solid Forms of Metformin Hydrochloride and Thiazide Diuretics
title_short	Synthesis, Characterization, and Intrinsic Dissolution Studies of Drug–Drug Eutectic Solid Forms of Metformin Hydrochloride and Thiazide Diuretics
title_full	Synthesis, Characterization, and Intrinsic Dissolution Studies of Drug–Drug Eutectic Solid Forms of Metformin Hydrochloride and Thiazide Diuretics
title_fullStr	Synthesis, Characterization, and Intrinsic Dissolution Studies of Drug–Drug Eutectic Solid Forms of Metformin Hydrochloride and Thiazide Diuretics
title_full_unstemmed	Synthesis, Characterization, and Intrinsic Dissolution Studies of Drug–Drug Eutectic Solid Forms of Metformin Hydrochloride and Thiazide Diuretics
title_sort	synthesis, characterization, and intrinsic dissolution studies of drug–drug eutectic solid forms of metformin hydrochloride and thiazide diuretics
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/3a70b6590cef4096b69afd6913f837f7
work_keys_str_mv	AT guadalupecoyotedotor synthesischaracterizationandintrinsicdissolutionstudiesofdrugdrugeutecticsolidformsofmetforminhydrochlorideandthiazidediuretics AT josecpaezfranco synthesischaracterizationandintrinsicdissolutionstudiesofdrugdrugeutecticsolidformsofmetforminhydrochlorideandthiazidediuretics AT danielcansecogonzalez synthesischaracterizationandintrinsicdissolutionstudiesofdrugdrugeutecticsolidformsofmetforminhydrochlorideandthiazidediuretics AT alejandranunezpineda synthesischaracterizationandintrinsicdissolutionstudiesofdrugdrugeutecticsolidformsofmetforminhydrochlorideandthiazidediuretics AT alejandrodorazcogonzalez synthesischaracterizationandintrinsicdissolutionstudiesofdrugdrugeutecticsolidformsofmetforminhydrochlorideandthiazidediuretics AT inesfuentesnoriega synthesischaracterizationandintrinsicdissolutionstudiesofdrugdrugeutecticsolidformsofmetforminhydrochlorideandthiazidediuretics AT alfredorvilchisnestor synthesischaracterizationandintrinsicdissolutionstudiesofdrugdrugeutecticsolidformsofmetforminhydrochlorideandthiazidediuretics AT joelisrodriguezhernandez synthesischaracterizationandintrinsicdissolutionstudiesofdrugdrugeutecticsolidformsofmetforminhydrochlorideandthiazidediuretics AT davidmoralesmorales synthesischaracterizationandintrinsicdissolutionstudiesofdrugdrugeutecticsolidformsofmetforminhydrochlorideandthiazidediuretics AT juanmanuelgermanacacio synthesischaracterizationandintrinsicdissolutionstudiesofdrugdrugeutecticsolidformsofmetforminhydrochlorideandthiazidediuretics
_version_	1718410765587709952

Synthesis, Characterization, and Intrinsic Dissolution Studies of Drug–Drug Eutectic Solid Forms of Metformin Hydrochloride and Thiazide Diuretics

Ejemplares similares