Razvoj metode in vitro oslobađanja djelatne tvari

undergraduate thesis

• Title (english): Development of in vitro drug release method
• Author: Veronika Žlabravec
• 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: 2019-09-18, Croatia
• Scientific / art field, discipline and subdiscipline: TECHNICAL SCIENCES; Chemical Engineering

Abstract

In vitro ispitivanje oslobađanja djelatne tvari provodi se prema definiranom postupku, propisanom od strane odgovarajućih regulatornih tijela, koji se posebno razvija za pojedinu djelatnu tvar. Ponekad je za jednu djelatnu tvar predloženo više metoda koje se razlikuju po namijenjenim medijima i/ili aparaturi. U ovom radu ispitana je ekvivalentnost i zamjenjivost dviju in vitro metoda oslobađanja za djelatnu tvar celekoksib, propisanih od strane Američke agencije za hranu i lijekove (FDA). Provedena su ispitivanja oslobađanja prema USP 2 metodi u dva različita medija: 1) otopini natrijeva fosfata s natrij lauril sulfatom te 2) želučanoj tekućini s pepsinom, natrijevim hidroksidom i natrij lauril sulfatom. Uzorci su analizirani na UV/Vis spektrofotometru. Dobivene koncentracije prikazane u ovisnosti o vremenu daju profile oslobađanja koje je bilo potrebno usporediti. Sličnost profila provjerena je usporedbom na tri načina: korištenjem metoda ovisnih o modelu, metoda neovisnih o modelu te statističkim usporedbenim metodama. Oba profila zadovoljavajuće se mogu opisati Korsmeyer-Peppasovim modelom čiji izračunati parametri ukazuju na međusobnu sličnost. Vrijednosti faktora sličnosti i faktora razlike te gotovo sve vrijednosti T-testa i statističke analize varijance također ukazuju na sličnost profila, a time i na ekvivalentnost metoda. U desetoj i dvadesetoj minuti, međutim, nulta hipoteza o sličnosti opovrgnuta je p-vrijednostima manjima od 0,05. Tada je, naime, količina oslobođene tvari u mediju 2 nezanemarivo veća od one u mediju 1.

Abstract (english)

In vitro drug release testing is performed according to a defined procedure enjoined by appropriate regulatory authorities and specifically developed for each active substance. In some cases, multiple methods of dissolution testing that vary in used media and/or apparatus are proposed for one active substance. This paper examines interchangeability of two FDA-recommended in vitro dissolution methods for the substance celecoxib. Dissolution tests were performed according to USP 2 method in two different media: 1) sodium phosphate solution with sodium lauryl sulfate and 2) simulated gastric fluid with pepsin, sodium hydroxide and sodium lauryl sulfate. Samples were analyzed using UV/Vis spectrophotometer. Dissolution profiles, shown as concentrations as a function of time, were compared. The similarity between the profiles was investigated using model-dependent, model-independent and statistical methods. Both profiles could be described adequately by the Korsmeyer-Peppas model, whose calculated parameters indicate similarity. The values of similarity and difference factors, as well as almost all values of the T-test and the statistical analysis of variance, also indicated the similarity of the profiles and thus the equivalence of two methods. The null hypothesis of similarity was, however, refuted at the tenth and twentieth minute by p-values less than 0.05. The amount of substance released in medium 2 was significantly greater than that in medium 1 at these time points.

• Keywords: celekoksib; in vitro ispitivanje; Korsmeyer-Peppasov model; statističke metode
• Keywords (english): celecoxib; in vitro testing; Korsmeyer-Peppas model; statistical methods
• Language: croatian
• URN:NBN: urn:nbn:hr:149:454385
• Study programme: Title: Chemical Engineering - Undergraduate study; Study programme type: university; Study level: undergraduate; Academic / professional title: sveučilišni/a prvostupnik/ prvostupnica (baccalaureus/baccalaurea) inženjer/inženjerka kemijskog inženjerstva (sveučilišni/a prvostupnik/ prvostupnica (baccalaureus/baccalaurea) inženjer/inženjerka kemijskog inženjerstva)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2023-05-29 13:23:50