Pedro Yuri Gerônimo Kobata, Julian Ticona Chambi, Ana Maria do Espirito Santo, Silvia Lucia Cuffini
{"title":"Eutectic mixtures containing the active pharmaceutical ingredient ezetimibe: Phase diagrams, solid state characterization and dissolution profiles","authors":"Pedro Yuri Gerônimo Kobata, Julian Ticona Chambi, Ana Maria do Espirito Santo, Silvia Lucia Cuffini","doi":"10.1016/j.jcrysgro.2024.127775","DOIUrl":null,"url":null,"abstract":"<div><p>Cardiovascular disease represents the leading cause of death worldwide, according to the World Health Organization (WHO) report. One of the treatment strategies is the use of the drug ezetimibe (EZT). This drug is a cholesterol absorption inhibitor with low aqueous solubility, which affects its therapeutic efficacy. The purpose of this paper was to obtain eutectic materials of EZT with methylparaben (MPB), salicylic acid (SCA) and nicotinamide (NTM) coformers, and to study their phase diagrams, dissolution properties and hygroscopicity to assess possible enhancements. Phase and Tamman diagrams were constructed using differential scanning calorimetry (DSC) results. The eutectic materials were characterized by powder X-ray diffraction (PXRD) and polarized light optical microscopy (OM). The hygroscopicity of the materials was assessed at different relative humidities (RH) through dynamic vapor sorption (DVS). The dissolution study was conducted with the materials in powder form, with paddle dissolution, rotating at 50 rpm, in 900 mL of aqueous buffer solution at pH 6.8 and 37 °C. The phase diagrams demonstrated that EZT formed eutectic systems with eutectic molar fractions of 0.59, 0.67 and 0.69 for EZT-SCA, EZT-NTM and EZT-MPB, respectively. The three eutectic materials are characterized as microcrystalline conglomerates of their components. In terms of the hygroscopic behavior of EZT at different RHs, eutectic materials demonstrated lower susceptibility to monohydrate formation compared to the anhydrous form. In dissolution studies, EZT-SCA and EZT-MPB solubilized EZT in amounts 22 % higher than the pure drug in 15 min. On the other hand, EZT-NTM eutectic suppressed the dissolution of EZT down to 56 % at the same time. The results indicated the possibility of obtaining materials with enhanced properties using eutectic mixtures, with improved dissolution rates and hygroscopic stability.</p></div>","PeriodicalId":353,"journal":{"name":"Journal of Crystal Growth","volume":null,"pages":null},"PeriodicalIF":1.7000,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Crystal Growth","FirstCategoryId":"88","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0022024824002100","RegionNum":4,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CRYSTALLOGRAPHY","Score":null,"Total":0}
引用次数: 0
Abstract
Cardiovascular disease represents the leading cause of death worldwide, according to the World Health Organization (WHO) report. One of the treatment strategies is the use of the drug ezetimibe (EZT). This drug is a cholesterol absorption inhibitor with low aqueous solubility, which affects its therapeutic efficacy. The purpose of this paper was to obtain eutectic materials of EZT with methylparaben (MPB), salicylic acid (SCA) and nicotinamide (NTM) coformers, and to study their phase diagrams, dissolution properties and hygroscopicity to assess possible enhancements. Phase and Tamman diagrams were constructed using differential scanning calorimetry (DSC) results. The eutectic materials were characterized by powder X-ray diffraction (PXRD) and polarized light optical microscopy (OM). The hygroscopicity of the materials was assessed at different relative humidities (RH) through dynamic vapor sorption (DVS). The dissolution study was conducted with the materials in powder form, with paddle dissolution, rotating at 50 rpm, in 900 mL of aqueous buffer solution at pH 6.8 and 37 °C. The phase diagrams demonstrated that EZT formed eutectic systems with eutectic molar fractions of 0.59, 0.67 and 0.69 for EZT-SCA, EZT-NTM and EZT-MPB, respectively. The three eutectic materials are characterized as microcrystalline conglomerates of their components. In terms of the hygroscopic behavior of EZT at different RHs, eutectic materials demonstrated lower susceptibility to monohydrate formation compared to the anhydrous form. In dissolution studies, EZT-SCA and EZT-MPB solubilized EZT in amounts 22 % higher than the pure drug in 15 min. On the other hand, EZT-NTM eutectic suppressed the dissolution of EZT down to 56 % at the same time. The results indicated the possibility of obtaining materials with enhanced properties using eutectic mixtures, with improved dissolution rates and hygroscopic stability.
期刊介绍:
The journal offers a common reference and publication source for workers engaged in research on the experimental and theoretical aspects of crystal growth and its applications, e.g. in devices. Experimental and theoretical contributions are published in the following fields: theory of nucleation and growth, molecular kinetics and transport phenomena, crystallization in viscous media such as polymers and glasses; crystal growth of metals, minerals, semiconductors, superconductors, magnetics, inorganic, organic and biological substances in bulk or as thin films; molecular beam epitaxy, chemical vapor deposition, growth of III-V and II-VI and other semiconductors; characterization of single crystals by physical and chemical methods; apparatus, instrumentation and techniques for crystal growth, and purification methods; multilayer heterostructures and their characterisation with an emphasis on crystal growth and epitaxial aspects of electronic materials. A special feature of the journal is the periodic inclusion of proceedings of symposia and conferences on relevant aspects of crystal growth.