prikaz prve stranice dokumenta Mehanokemijska priprava i karakterizacija polimernih disperzija i kokristala prazikvantela
  Download
PDF 5.3 MB
doctoral thesis
Mehanokemijska priprava i karakterizacija polimernih disperzija i kokristala prazikvantela
Zagreb: University of Zagreb, Faculty of Science, 2019. urn:nbn:hr:217:429428
Cugovčan, Martina
University of Zagreb
Faculty of Science
Department of Chemistry

Institutional repository: Repository of the Faculty of Science

Cite this document

Cugovčan, M. (2019). Mehanokemijska priprava i karakterizacija polimernih disperzija i kokristala prazikvantela (Doctoral thesis). Zagreb: University of Zagreb, Faculty of Science. Retrieved from https://urn.nsk.hr/urn:nbn:hr:217:429428

Cugovčan, Martina. "Mehanokemijska priprava i karakterizacija polimernih disperzija i kokristala prazikvantela." Doctoral thesis, University of Zagreb, Faculty of Science, 2019. https://urn.nsk.hr/urn:nbn:hr:217:429428

Cugovčan, Martina. "Mehanokemijska priprava i karakterizacija polimernih disperzija i kokristala prazikvantela." Doctoral thesis, University of Zagreb, Faculty of Science, 2019. https://urn.nsk.hr/urn:nbn:hr:217:429428

Cugovčan, M. (2019). 'Mehanokemijska priprava i karakterizacija polimernih disperzija i kokristala prazikvantela', Doctoral thesis, University of Zagreb, Faculty of Science, accessed 21 December 2024, https://urn.nsk.hr/urn:nbn:hr:217:429428

Cugovčan M. Mehanokemijska priprava i karakterizacija polimernih disperzija i kokristala prazikvantela [Doctoral thesis]. Zagreb: University of Zagreb, Faculty of Science; 2019 [cited 2024 December 21] Available at: https://urn.nsk.hr/urn:nbn:hr:217:429428

M. Cugovčan, "Mehanokemijska priprava i karakterizacija polimernih disperzija i kokristala prazikvantela", Doctoral thesis, University of Zagreb, Faculty of Science, Zagreb, 2019. Available at: https://urn.nsk.hr/urn:nbn:hr:217:429428

Metadata
TitleMehanokemijska priprava i karakterizacija polimernih disperzija i kokristala prazikvantela
Title (english)Mechanochemical preparation and characterization of polymeric dispersions and cocrystals of praziquantel
AuthorMartina Cugovčan
MentorNives Galić (mentor)
MentorMario Jug (komentor)
Committee memberDominik Cinčić (predsjednik povjerenstva)
Committee memberNives Galić (član povjerenstva)
Committee memberJasna Jablan (član povjerenstva)
GranterUniversity of Zagreb
Faculty of Science
(Department of Chemistry)
Zagreb
Defense date and country2019-11-28, Croatia
Scientific / art field,
discipline and subdiscipline		NATURAL SCIENCES
Chemistry
Universal decimal classification
(UDC)		54 - Chemistry. Crystallography. Mineralogy
Abstract
Mehanokemijska aktivacija mljevenjem uz dodatak različitih aditiva korištena je s ciljem poboljšanja nepovoljnih fizičkokemijskih i biofarmaceutskih svojstava prazikvantela (PZQ). Mljevenjem PZQ s limunskom (CA), jabučnom (MA), salicilnom (SA) i vinskom kiselinom (TA) pripravljeni su kokristali za koje je ustanovljeno da topljivost i brzina otapanja ovisi o pH. Najtopljiviji kokristal PZQ s MA kemijski je nestabilan. Najveće povećanje topljivosti i brzine otapanja uočeno je za ekvimolarne komplekse prazikvantela s amorfnim hidroksipropil--ciklodekstrinom (HPβCD) i nasumično metiliranim -ciklodekstrinom (MβCD), ali je jedino produkt PZQ/HPβCD pokazao prihvatljivu kemijsku stabilnost i fotostabilnost. Mljevenjem lijeka s MA i HPβCD u ekvimolarnim količinama također su pripravljeni topljivi amorfni produkti koji su bili kemijski nestabilni, a time neprikladni za farmaceutsku primjenu. Ispitivanja na Caco-2 monosloju potvrdila su biokompatibilnost kompleksa PZQ/HPβCD te da kompleksiranje nije utjecalo na intrinsičnu permeabilnost prazikvantela Papp(PZQ)=(3,72±0,33)10–5 cm s–1 i Papp(PZQ/HPβCD)=(3,65±0,21)10–5 cm s–1; p>0,05).
Abstract (english)
Mechanochemical activation using different co-grinding additives was applied to improve physiochemical and biopharmaceutical properties of praziquantel (PZQ). Liquid assisted grinding with citric (CA), malic (MA), salicylic (SA) and tartaric acid (TA) gained in cocrystal formation, which all showed pH-dependent solubility and dissolution rate. The most soluble cocrystal of PZQ with MA was chemically unstable, as seen during the stability testing. Equimolar praziquantel complexes with amorphous hydroxypropyl-β-cyclodextrin (HPβCD) and randomly methylated β-cyclodextrin (MβCD) showed the highest improvement in drug solubility and the dissolution rate, but only PZQ/HPβCD product presented an acceptable chemical and photostability profile. Co-grinding the drug with both MA and HPβCD in equimolar ratio, also gave highly soluble amorphous product which was chemical instable and therefore not suitable for the pharmaceutical use. Studies on Caco-2 monolayer confirmed the biocompatibility of PZQ/HPβCD complex and showed that complexation did not adversely affect the intrinsically high PZQ permeability Papp(PZQ)=(3.72±0.33)10–5 cm s–1 and Papp(PZQ/HPβCD)=(3.65±0.21)10–5 cm s–1; p>0.05).
Keywords
Keywords (english)
Languagecroatian
URN:NBNurn:nbn:hr:217:429428
Study programmeTitle: Doctoral study in chemistry
Study programme type: university
Study level: postgraduate
Academic / professional title: doktor/doktorica znanosti, područje prirodnih znanosti, polje kemija (doktor/doktorica znanosti, područje prirodnih znanosti, polje kemija)
Type of resourceText
Extent98 str. ; 30 cm
File originBorn digital
Access conditionsOpen access
Terms of useLicence In copyright icon
Created on2019-12-18 11:38:59