Priprava i primjena koprocesiranih pomoćnih tvari

master's thesis

• Title (english): Preparation and application of co-processed excipients
• Author: Lucija Svorcina
• Mentor: Krunoslav Žižek (mentor)
• Committee member: Krunoslav Žižek (predsjednik povjerenstva)
• Committee member: Marin Kovačić (član povjerenstva)
• Committee member: Katarina Mužina (član povjerenstva)
• Granter: University of Zagreb; Faculty of Chemical Engineering and Technology; Zagreb
• Defense date and country: 2024-07-05, Croatia
• Scientific / art field, discipline and subdiscipline: TECHNICAL SCIENCES; Chemical Engineering

Abstract

Ovaj rad bavi se problemom poboljšanja topljivosti i bioraspoloživosti dasatiniba, koji se koristi za liječenje leukemije. Dasatinib ima ograničenu topljivost u vodenom mediju, što rezultira slabom i sporom apsorpcijom u gastrointestinalnom traktu te niskom bioraspoloživošću. Modifikacija topljivosti i oslobađanja dasatiniba može imati pozitivan utjecaj na oralnu apsorpciju i bioraspoloživost lijeka. Glavni cilj istraživanja je formulirati ovaj specifičan lijek primjenom koprocesirane pomoćne tvari. Koprocesirana pomoćna tvar pripravljena je mehanokemijskim tretmanom i granuliranjem taljenjem. Pripremljena čvrsta disperzija pomoćnih tvari karakterizirana je metodama analize koje mogu ukazati na uspješnu pripravu disperzija. Pripravljena disperzija, odnosno koprocesirana pomoćna tvar, korištena je u pripravi konačnog dozirnog oblika djelatne tvari, tableta. Mehanokemijskim tretmanom nije ostvarena željena amorfizacija pomoćnih tvari. Granuliranjem taljenjem pripravljene su čvrste disperzije mikrokristalne celuloze, D-manitola i poli(etilen-glikola). Provedena je morfološka i granulometrijska analiza pripravljenih uzoraka. Pripravljene tablete testirane su na ujednačenost masa i sadržaja, čvrstoću, raspadljivost te topljivost. Koprocesiranjem pomoćnih tvari modificiran je profil oslobađanja dasatiniba.

Abstract (english)

This thesis addresses the issue of improving the solubility and bioavailability of dasatinib, which is used to treat leukemia. Dasatinib has limited solubility in aqueous media, resulting in slow and poor absorption in the gastrointestinal tract and low bioavailability. Changing the solubility and release of dasatinib could have a positive effect on the oral absorption and bioavailability of the drug. The main objective of the research is to formulate this specific drug using a co-processed excipient. The co-processed excipient is prepared by mechanochemical treatment and melt granulation. The prepared solid dispersion of excipients was characterized using analytical methods that can give an indication of the successful preparation of dispersions. The prepared dispersion, i.e. the co-processed excipient, was used to prepare the final dosage form of the drug, the tablets. The desired amorphization of the excipients was not achieved by the mechanochemical treatment. Solid dispersions of microcrystalline cellulose, D-mannitol and poly(ethylene glycol) were prepared by melt granulation. Morphological and granulometric analysis of the prepared samples was carried out. The prepared tablets were tested for uniformity of mass and content, hardness, disintegration and solubility. The release profile of dasatinib was modified by co-processing of excipients.

• Keywords: dasatinib; poboljšanje svojstva lijeka; koprocesirana pomoćna tvar; mehanokemijska priprava; granuliranje taljenjem; oslobađanje djelatne tvari
• Keywords (english): dasatinib; drug property improvement; co-processed excipient; mechanochemical preparation; melt granulation; drug release
• Language: croatian
• URN:NBN: urn:nbn:hr:149:751663
• Study programme: Title: Environmental Engineering - Graduate study; Study programme type: university; Study level: graduate; Academic / professional title: sveučilišni/a magistar/magistra inženjer/inženjerka ekoinženjerstva (sveučilišni/a magistar/magistra inženjer/inženjerka ekoinženjerstva)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2024-07-08 09:23:47