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Optimizacija uslova dobijanja mikrosfera na bazi biodegradabilnog poli(ε-kaprolaktona) za kontrolisano otpuštanje karbamazepina

dc.creatorPepić, Dragana
dc.creatorAnđelković, Darinka R.
dc.creatorNikolić, Marija
dc.creatorGrujić, Svetlana
dc.creatorĐonlagić, Jasna
dc.date.accessioned2021-03-10T11:20:12Z
dc.date.available2021-03-10T11:20:12Z
dc.date.issued2010
dc.identifier.issn0367-598X
dc.identifier.urihttp://TechnoRep.tmf.bg.ac.rs/handle/123456789/1656
dc.description.abstractPoly (ε-caprolactone), PCL, is an aliphatic polyester suitable for controlled drug release due to its biodegradability, biocompatibility, non-toxicity and high permeability to many therapeutic drugs. This study investigates the effect of the preparation parameters on the size and the morphology of the PCL microspheres and on the release profile of carbamazepine from these microspheres. The PCL microspheres were prepared using oil-in-water (o/w) emulsion solvent evaporation method with the poly(vinyl alcohol), PVA, as the emulsion stabilizer. The influence of the stirring rate applied during the emulsion formation, the homogenization time and the emulsifier concentration on diameter and size distribution of the microspheres was analyzed by scanning electron microscope (SEM). The initial emulsion was formed applying high stirring rates of 10000, 18000 and 23000 rpm, for homogenization times: 5, 10 and 15 min. The diameter was strongly influenced by the stirring rate, and the average particle size decreased from 9.2 to 2.8 ìm with the increase of the stirring rate. Increasing the amount of PVA in the water phase from 0.2 to 1 mass% improved stabilization of the oil droplets and led to a slight decrease of the average particle diameter. Drug-loaded microspheres were prepared by the same technique using different amounts of carbamazepine (10 and 15 mass%), under given conditions (1.0 mass% PVA, stirring rate of 18000 rpm for a period of 5 min of emulsion formation). Additionally, microspheres were prepared by applying low stirring rate of 1000 rpm with 10 and 15 mass% of the drug. The SEM analysis showed that microspheres created with 18000 rpm stirring rate, had average diameters of 3-4 ìm, and the microspheres prepared with 1000 rpm stirring rate were larger than 100 ìm. It was also observed that, in the case of the large microspheres, carbamazepine was deposited on their surfaces, while the small microspheres had smooth surfaces without observable drug crystals. The encapsulation efficiency and the release behaviour of the carbamazepine were examined using high performance liquid chromatography-ultraviolet spectroscopy (HPLC-UV). The drug encapsulation efficiencies were in the range from 69 to 81%, and were increasing with the increase of the amount of carbamazepine in both series. In vitro release experiments were carried out in the phosphate buffer solution (pH 7) at 37°C. The release rate was influenced by the microspheres size and morphology. The larger microspheres released more carbamazepine (85-95%) compared to the small ones (50-65%) for the same period. This behavior was attributed to the different drug distribution in the PCL matrix. Different mathematical models were used to describe drug release kinetics. It was concluded that the mechanism of the carbamazepine release from the microspheres was diffusion-controlled, independent on the type of microspheres. The kinetic parameters showed that the release of carbamazepine was slower from the smaller microspheres, probably as a result of more even distribution of the drug in the polymer matrix.en
dc.description.abstractCilj ovog rada je ispitivanje uticaja uslova dobijanja mikrosfera biodegradabilnog poli(ε-kaprolaktona) tehnikom otparavanja rastvarača iz emulzije, na veličinu i raspodelu veličina mikrosfera. Polazne emulzije rastvora polimera u vodi formirane su pri velikim brzinama mešanja tokom formiranja emulzije u opsegu od 10000 do 23000 o min-1, radi dobijanja mikrosfera malih prečnika. Varirana je brzina mešanja prilikom formiranja emulzije, dužina trajanja emulgovanja velikim brzinama mešanja i udeo stabilizatora emulzije, poli(vinil alkohola). Veličina i raspodela veličina polimernih mikrosfera određivana je skenirajućom elektronskom mikroskopijom. U polimerne mikrosfere inkapsuliran je lek karbamazepin iz grupe antiepileptika i određivana je efikasnost inkapsulacije, kao i profil otpuštanja leka u puferskom rastvoru metodom tečne hromatografije sa UV spektroskopijom. Takođe je izučavana kinetika otpuštanja karbamazepina korišćenjem različitih modela s ciljem ispitivanja mehanizma otpuštanja leka iz mikrosfera dobijenih pri različitim uslovima.sr
dc.publisherAssociation of Chemical Engineers of Serbia
dc.relationinfo:eu-repo/grantAgreement/MESTD/MPN2006-2010/142023/RS//
dc.relationinfo:eu-repo/grantAgreement/MESTD/MPN2006-2010/142002/RS//
dc.rightsopenAccess
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.sourceHemijska industrija
dc.subjectmicrospheres preparationen
dc.subjectpoly(ε-caprolactone)en
dc.subjectemulsion solvent evaporation methoden
dc.subjectin vitro drug releaseen
dc.subjectcarbamazepineen
dc.subjectizrada mikrosferasr
dc.subjectpoli(ε-kaprolakton)sr
dc.subjectemulzioni postupak uz otparavanje rastvaračasr
dc.subjectin vitro otpuštanje lekasr
dc.subjectkarbamazepinsr
dc.titleOptimization of preparation conditions of poly(ε-caprolactone) microspheres for controlled release of carbamazepineen
dc.titleOptimizacija uslova dobijanja mikrosfera na bazi biodegradabilnog poli(ε-kaprolaktona) za kontrolisano otpuštanje karbamazepinasr
dc.typearticle
dc.rights.licenseBY-NC-ND
dc.citation.epage502
dc.citation.issue6
dc.citation.other64(6): 491-502
dc.citation.rankM23
dc.citation.spage491
dc.citation.volume64
dc.identifier.doi10.2298/HEMIND101117073P
dc.identifier.fulltexthttp://TechnoRep.tmf.bg.ac.rs/bitstream/id/8638/0367-598X1000073P.pdf
dc.identifier.scopus2-s2.0-78651251192
dc.identifier.wos000287224600002
dc.type.versionpublishedVersion


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