Razvoj in vitro metode za ispitivanje brzine oslobađanja deksametazona iz topikalne nanosuspenzije

master's thesis

• Title (english): Development of an analytical method for in vitro release testing of dexamethasone nanosuspensions
• Author: Antonia Šutić
• Mentor: Biserka Cetina Čižmek (mentor)
• Committee member: Biserka Cetina Čižmek (predsjednik povjerenstva)
• Committee member: Anita Hafner (član povjerenstva)
• Committee member: Jasmina Lovrić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; Zagreb
• Defense date and country: 2016-08-30, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Postoji interes za razvojem pripravaka deksametazona kojima bi se postiglo ciljano lokalno djelovanje lijeka na oboljelom mjestu te ujedno smanjila pojavnost sistemskih nuspojava te izbjegao prvi prolazak kroz jetru. Za topikalnu primjenu deksametazona potrebno je razviti prikladan terapijski sustav koji bi omogućio produženo i kontrolirano oslobađanje lijeka.
Cilj ovog rada je razvoj i usporedba analitičkih metoda za ispitivanje oslobađanja djelatne tvari deksametazona iz nanočestičnih terapijskih sustava za topikalnu primjenu korištenjem triju aparatura za ispitivanje oslobađanja (imerzijska ćelija, vertikalna difuzijska ćelija i dijalizacijske vrećice), te uzimajući u obzir fiziološke uvjete na mjestu primjene ovakvih terapijskih sustava. Difuzija lijeka odvijala se preko polietersulfonske membrane, odnosno dijalizacijske celulozne membrane, koje su pokazale nisku adsorpciju lijeka te nizak otpor difuziji lijeka. Nakon početnog zastojnog vremena količina oslobođenog lijeka postala je proporcionalna korijenu iz vremena. Nagib u linearnom području krivulje oslobađanja lijeka korišten je kao mjera brzine oslobađanja.
Metoda s imerzijskim ćelijama se s obzirom na demonstriranu diskriminatornost i ponovljivost pokazala kao najbolja metoda za ispitivanje oslobađanja deksametazona iz nanosuspenzije.
Iako se metoda s dijalizacijskim vrećicama pokazala dovoljno osjetljivom za ispitane parametre, uočena je velika varijabilnost (RSD) u rezultatima.
Vertikalna difuzijska ćelija nije pokazala dovoljnu osjetljivost za ovakvu vrstu uzoraka zbog male površine membrane s koje se događa difuzija ljekovite tvari.

Abstract (english)

There has been an increasing focus on development of new routes of dexamethasone administration to provide targeting of the drug for local action, and also to reduce systemic side effects and avoid the first pass metabolism through the liver. For topical administration of dexamethasone is necessary to develop an appropriate therapeutic system that would enable sustained and controlled release of the drug.
The aim of this study was to develop and compare the analytical methods for in vitro release testing of the active substance dexamethasone from nanoparticle-based therapeutic system using three apparatuses for in vitro release testing of topical formulations (imersion cell, vertical diffusion cell and dialysis bag membrane method), taking into account the physiological conditions at the point of application of these therapeutic systems. Diffusion of the drug occured across polyethersulfone membrane, or across dialysis cellulose membrane, which demonstrated low drug adsorption and low diffusional resistance. After an initial lag phase the amount of drug released became proportional to the square root of time. The slope in the linear portion of the release curve was used as a measure of release rate.
The imersion cell method was found to have the best discriminatory power and repetability for in vitro release testing of dexamethasone from nanosuspension.
Although the dialysis bag membrane method revealed sufficiently sensitive to the tested parameters, great variability (RSD) in the results was observed.
The vertical diffusion cell did not show sufficient sensitivity to this type of samples due to the small surface of the membrane across which the diffusion of the therapeutic agent occurs.

• Keywords: deksametazon; nanosuspenzija; ispitivanje in vitro oslobađanja; imerzijska ćelija; vertikalna difuzijska ćelija; dijalizacijske vrećice
• Keywords (english): dexamethasone; nanosuspension; in vitro release testing; imersion cell; vertical diffusion cell; dialysis bag membrane method
• Language: croatian
• URN:NBN: urn:nbn:hr:163:546022
• Study programme: Title: Pharmacy; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: magistar/magistra farmacije (magistar/magistra farmacije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Access restricted to students and staff of home institution
• Created on: 2016-11-29 16:37:01