Ekstrudiranje taljenjem kao metoda povećanja topljivosti djelatne tvari

master's thesis

• Title (english): Hot-melt extrusion as a method for improvement of drug solubility
• Author: Marina Štokić
• Mentor: Gordana Matijašić (mentor)
• Committee member: Gordana Matijašić (predsjednik povjerenstva)
• Committee member: Krunoslav Žižek (član povjerenstva)
• Committee member: Juraj Šipušić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Chemical Engineering and Technology; Zagreb
• Defense date and country: 2019-09-27, Croatia
• Scientific / art field, discipline and subdiscipline: TECHNICAL SCIENCES; Chemical Engineering

Abstract

Glavni izazov u formuliranju farmaceutskih oralnih oblika leži u slaboj bioraspoloživosti lijeka koja se najčešće pripisuje njegovoj slaboj topljivosti. Odabir metode poboljšanja topljivosti ovisi o svojstvima lijeka, mjestu apsorpcije i potrebnim karakteristikama dozirnog oblika. Zadatak ovog rada je povećanje topljivosti djelatne tvari, celekoksiba, metodom ekstrudiranja taljenjem. U eksperimentu su za dobivanje ekstrudata korišteni Soluplus, poli(etilen-glikol) (PEG) te celekoksib kao djelatna tvar. Pripremljene su mješavine te dobiveni ekstrudati pri određenim temperaturama (CLX-SOL-170, CLX-SOL-120 i CLX-PEG-57-61). Pripremljenim uzorcima ispitan je sadržaj, topljivost, profili oslobađanja te su provedene DSC i XRD metode karakterizacije. Topljivost je provedena tzv. metodom potresanja te ispitana UV/Vis spektrofotometrijom. In vitro ispitivanje otpuštanja celekoksiba provedeno je u USP2 uređaju prema propisanim uvjetima. Sve korištene tvari, fizičke mješavine i ekstrudati analizirani su DSC i XRD metodama karakterizacije. Primjenom programskog dodatka DDSolvera, odnosno metodom usporedbe parova – faktorom sličnosti i faktorom razlike uspoređeni su profili otpuštanja djelatne tvari. Rezultati su pokazali uspješnost u povećanju topljivosti, kao i brzine otpuštanja celekoksiba. Zaključno, prema dobivenim rezultatima pokazalo se da je najveće povećanje topljivosti dobiveno uz Soluplus pri temperaturi ekstruzije od 170 °C (CLX-SOL-170). Kao potvrda tomu, XRD difraktogramima je utvrđen amorfni oblik CLX što direktno utječe na njegovu topljivost.

Abstract (english)

The main challenge in the formulation of pharmaceutical oral dosage forms lies in the low bioavailability of the drug, which is most often attributed to its poor solubility. Selection of solubility improving method depends on drug property, site of absorption, and required dosage form characteristics. The aim of the work described in this thesis is to increase the solubility of the active substance, celecoxib, by using hot melt extrusion (HME) technique. To obtain extrudates, in the experiment were used Soluplus, poly(ethylene glycol) (PEG) and celecoxib as the active substance. Mixtures were prepared and extrudates were obtained at certain temperatures (CLX-SOL-170, CLX-SOL-120 and CLX-PEG-57-61). The prepared samples were analysed for their content, solubility, release profiles and characterized by DSC and XRD methods. Solubility was measured by using the so-called shake-flask method and tested by using UV/Vis spectrophotometer. In vitro testing of celecoxib release was studied in USP 2 device under prescribed conditions. All substances used, physical mixtures and extrudates were analyzed by using DSC and XRD characterization methods. By applying DDSolver, an Excel add-in software package, i.e. the pairwise comparison method – the release profiles of the active substance were compared by using the similarity factor and the difference factor. The results showed that solubility and release rates of celecoxib successfully increased. In conclusion, according to the results obtained, it was shown that the highest solubility was achieved with Soluplus at the extrusion temperature of 170°C (CLX-SOL-170). To confirm this, the amorphous structure of the resulting extrudate, which directly affects the solubility, was determined by using XRD methods.

• Keywords: celekoksib; topljivost; ekstrudiranje taljenjem; Soluplus; faktor razlike; faktor sličnosti
• Keywords (english): celecoxib; solubility; hot melt extrusion (HME); Soluplus; difference factor; similarity factor
• Language: croatian
• URN:NBN: urn:nbn:hr:149:928172
• Study programme: Title: Chemical Engineering - Graduate study; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra inženjer/inženjerka kemijskog inženjerstva (magistar/magistra inženjer/inženjerka kemijskog inženjerstva)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2022-02-27 16:22:42