Farmaceitiski aktīvo cietvielu florafūra un teofilīna šķīdinātāja veicinātas cietfāžu pārejas
Date
2015
Authors
Bobrovs, Raitis
Journal Title
Journal ISSN
Volume Title
Publisher
Latvijas Universitāte
Abstract
Darbā pilnveidota puskvantitatīva metode nelielu termodinamiski stabilās formas piemaisījumu daudzumu kvantificēšanai metastabilajā formā. Optimizējot paraugu sagatavošanas metodi, iespējams noteikt līdz 0,0005% termodinamiski stabilās formas metastabilajā formā. Apskatīta šķīdinātāja ietekme uz metodes jutību un, pētot šķīdinātāja desorbciju no parauga virsmas, raksturota šķīdinātāja un analizētā parauga virsmas mijiedarbība. Aprakstītas šķīdinātāja veicinātas fāžu pārejas no ftorafūra α uz β forumu un no teofilīna II uz IV formu. Noskaidrots, ka šķīdinātāja veicinātas fāžu pārejas no ftorafūra α formas uz β formu ātruma konstante ir lineāri atkarīga no pārsātinājuma pakāpes. Teofilīna IV formas rašanos kavē teofilīna molekulu paš-asociātu veidošanās protonu donoros šķīdinātājos.
Here we have improved a semi-quantitative method for low-level thermodynamically stable polymorph determination in the metastable polymorph. Optimization of sample preparation methodology and conditions lowered the detection limit down to 0.0005% of thermodynamically stable form in the metastable form. Solvent effect on sample preparation have been investigated and the nature of the solvent and surface interaction have been characterized using data from solvent desorption studies. Solvent mediated phase transformations (SMPTs) from α to β tegafur and theophylline form II to IV have been studied and characterized. It was determined that SMPT rate depend linearly on the supersaturation level. It was revealed that theophylline self-associates in H-bond donor solvents and the presence of these aggregates hinder the nucleation.
Here we have improved a semi-quantitative method for low-level thermodynamically stable polymorph determination in the metastable polymorph. Optimization of sample preparation methodology and conditions lowered the detection limit down to 0.0005% of thermodynamically stable form in the metastable form. Solvent effect on sample preparation have been investigated and the nature of the solvent and surface interaction have been characterized using data from solvent desorption studies. Solvent mediated phase transformations (SMPTs) from α to β tegafur and theophylline form II to IV have been studied and characterized. It was determined that SMPT rate depend linearly on the supersaturation level. It was revealed that theophylline self-associates in H-bond donor solvents and the presence of these aggregates hinder the nucleation.
Description
Elektroniskā versija nesatur pielikumus
Keywords
Ķīmija , Ķīmija, ķīmijas tehnoloģijas un biotehnoloģija