Pulvera rentgendifrakcijas un aprēķinu metožu izmantošana izvēlētu farmaceitiski aktīvu vielu polimorfo formu strukturālajiem pētījumiem
Date
2021
Authors
Kons, Artis
Journal Title
Journal ISSN
Volume Title
Publisher
Latvijas Universitāte
Abstract
Darbā pētītas vairākas farmaceitiski aktīvas vielas, kas izvēlētas, pamatojoties uz to spēju veidot daudzas sīkkristāliskas polimorfās formas. Izpētīta šo savienojumu kristālisko cietfāžu daudzveidība, veicot polimorfo formu un solvātu/hidrātu iegūšanu no dažādiem šķīdinātājiem. Iegūtās kristāliskās cietfāzes raksturotas ar rentgendifraktometriju, termiskās analīzes metodēm un dažādiem fāžu stabilitātes raksturošanas paņēmieniem. No pulvera rentgendifrakcijas datiem noteiktas 33 mikrokristālisku polimorfu un saistītu solvātu struktūras. Kristālisko struktūru optimizācijai, validācijai un enerģijas aprēķiniem pielietota dispersijas koriģēta blīvuma funkcionāļa teorija. Kristāliskās struktūras informācija izmantota, lai racionalizētu iegūto polimorfu veidošanos, fāžu pārejas un savstarpējo termodinamisko stabilitāti. Polimorfisms, termodinamiskā stabilitāte, mikrokristālisks pulveris, pulvera rentgendifraktometrija, struktūru noteikšana, dispersijas koriģēta blīvuma funkcionāļa teorija.
Several active pharmaceutical solids with abundant microcrystalline polymorphism have been studied. Screening of polymorphs and solvates/hydrates was carried out using crystallization from various solvents and by solid state transformation at different temperatures and relative humidity conditions. Stability and phase transformations among the obtained crystalline forms were investigated by X-ray powder diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetry analysis (TGA), and dynamic vapor sorption analysis. Slurry-bridging experiments at ambient temperature were carried out to ascertain the relative thermodynamic stability of the polymorphs. Crystal structures of 33 microcrystalline polymorphs have been determined from powder diffraction data. Crystal structure optimization and validation was carried out using dispersion corrected density functional theory (DFT-D) calculations. Crystal structure information is used to explain and rationalize the formation, phase transition and relative stability of polymorphs. Polymorphism, thermodynamic stability, microcrystalline powder, X-ray powder diffraction, structure determination, dispersion corrected density functional theory
Several active pharmaceutical solids with abundant microcrystalline polymorphism have been studied. Screening of polymorphs and solvates/hydrates was carried out using crystallization from various solvents and by solid state transformation at different temperatures and relative humidity conditions. Stability and phase transformations among the obtained crystalline forms were investigated by X-ray powder diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetry analysis (TGA), and dynamic vapor sorption analysis. Slurry-bridging experiments at ambient temperature were carried out to ascertain the relative thermodynamic stability of the polymorphs. Crystal structures of 33 microcrystalline polymorphs have been determined from powder diffraction data. Crystal structure optimization and validation was carried out using dispersion corrected density functional theory (DFT-D) calculations. Crystal structure information is used to explain and rationalize the formation, phase transition and relative stability of polymorphs. Polymorphism, thermodynamic stability, microcrystalline powder, X-ray powder diffraction, structure determination, dispersion corrected density functional theory
Description
Keywords
Ķīmija , Fizikālā ķīmija , Physical chemistry , Publikāciju kopa