Utjecaj formulacije lijeka na otpuštanje djelatne tvari

master's thesis

• Title (english): Effect of drug formulation on release of the active substance
• Author: Nikolina Malekinušić
• Mentor: Krunoslav Žižek (mentor)
• Committee member: Krunoslav Žižek (predsjednik povjerenstva)
• Committee member: Gordana Matijašić (član povjerenstva)
• Committee member: Zvjezdana Findrik Blažević (član povjerenstva)
• Granter: University of Zagreb; Faculty of Chemical Engineering and Technology; Zagreb
• Defense date and country: 2018-06-28, Croatia
• Scientific / art field, discipline and subdiscipline: TECHNICAL SCIENCES; Chemical Engineering; Mechanical, Thermal and Separation Processes

Abstract

Ovim istraživanjem pripremljene su konvencionalne i raspadljive tablete za usta s lurasidon hidrokloridom (LRD HCl) kao djelatnom tvari. U izradi tableta dobrih primjenskih svojstava korištene su procesne tehnologije granuliranja u fluidiziranom sloju tehnikom in-situ taljenja, oblaganja u fluidiziranom sloju i tabletiranja. U formulaciji lijeka korištene su pomoćne tvari: manitol, mikrokristalna celuloza te laktoza monohidrat kao punila; natrijeva kroskarmeloza kao sredstvo za raspadanje, magnezijev stearat kao lubrikant te polietilen glikol 4000 Da kao vezivo. Sredstvo za raspadanje ugrađeno je u matricu tablete granuliranjem i oblaganjem u fluidiziranom sloju. Pripremljene matrice tableta karakterizirane su testiranjem masa, tvrdoća i raspadljivosti tableta, te snimanjem profila otpuštanja djelatne tvari. Ispitan je utjecaj formulacije lijeka i načina ugradnje sredstva za raspadanje na primjenska svojstva tablete. Primjenom programskog dodatka DDSolvera analizirani su profili otpuštanja LRD HCl iz konvencionalnih i raspadljivih tableta za usta. Testirana je primjenjivost postojećih modela u opisu profila otpuštanja LRD HCl. Kinetika otpuštanja LRD HCl iz pripremljenih matrica tableta opisana je modelom nultog reda s vremenom odgode otpuštanja te Korsemeyer-Peppas modelom. Dobiveni eksponenti modela ukazuju na prisutne mehanizme otpuštanja LRD HCl iz matrica raspadljivih tableta.

Abstract (english)

With this study, conventional and orally disintegrated tablets have been prepared with lurasidone hydrochloride as an active pharmaceutical ingredient. Process technologies of in-situ fluidized bed melt granulation, fluidized bed coating and tabletting have been used for preparation of tablets with good end-use properties. Excipients used in drug formulation are: mannitol, microcrystalline cellulose and lactose monohydrate as fillers; croscarmellose sodium as a disintegrant; magnesium stearate as a lubricant and polyethylene glycol 4000 Da as a binder. Disintegrant has been embedded in a tablet matrix using fluidized bed granulation and coating. Prepared tablet matrices are characterized by testing the mass, hardness and the disintegration of the tabs and by recording the drug release profiles. The effect of drug formulation and the way for embedding the disintegrant on the end-use properties of a tablet has been studied. Lurasidone release profiles from conventional and orally disintegrated tablets are analysed using DDSolver add-in program. Available models have been tested to describe the release profiles of LRD HCl. The drug release kinetics for LRD HCl from prepared tablet matrices is described with zero-order model with lag time prior to drug release and by Korsemeyer-Peppas model. Derived model exponents indicate the mechanisms for lurasidone release from the disintegrated tablet matrices.

• Keywords: konvencionalna tableta; raspadljiva tableta za usta; lurasidon hidroklorid; raspadljivost tablete; otpuštanje djelatne tvari
• Keywords (english): conventional tablet; orally disintegrated tablet; lurasidone hydrochloride; tablet disintegration; drug release
• Language: croatian
• URN:NBN: urn:nbn:hr:149:368475
• 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: 2020-05-07 13:11:56