Priprema raspadljivih tableta za usta primjenom liofilizacije

master's thesis

• Title (english): Preparation of orally disintegrating tablets using lyophilization
• Author: Iva Gavran
• Mentor: Krunoslav Žižek (mentor)
• Committee member: Krunoslav Žižek (predsjednik povjerenstva)
• Committee member: Irena Škorić (član povjerenstva)
• Committee member: Anamarija Rogina (član povjerenstva)
• Granter: University of Zagreb; Faculty of Chemical Engineering and Technology; Zagreb
• Defense date and country: 2018-09-28, Croatia
• Scientific / art field, discipline and subdiscipline: TECHNICAL SCIENCES; Chemical Engineering; Mechanical, Thermal and Separation Processes

Abstract

U okviru ovog istraživanja pripremljene su raspadljive minitablete za usta s djelatnom tvari, Lurasidon hidrokloridom. Karakterizira ju loša topljivost, a time i loša bioraspoloživost lijeka. Topljivost se nastojala povećati pripremom čvrste disperzije primjenom liofilizacije, odnosno sušenja smrzavanjem pri čemu se djelatna tvar nastojala ugraditi u hidrofilnu polimernu matricu, polietilen glikola 4000. Tri uzorka s različitim udjelima djelatne i pomoćne tvari tretirana su liofilizacijom. Dobiveni liofilizati karakterizirani su sadržajem vlage, diferencijalnom pretražnom kalorimetrijom, rendgenskom difrakcijskom praha i infracrvenom spektroskopijom. Pripremljene su četiri formulacije lijeka primjenom procesnih tehnologija liofilizacije, granuliranja i tabletiranja. Tri formulacije lijeka pripravljene su s liofilizatima Lurasidon hidroklorida i polietilen glikola te granulatom pomoćnih tvari, dok je četvrta pripremljena granuliranjem djelatne tvari i pomoćnih tvari u fluidiziranom sloju in situ taljenjem. Korištene pomoćne tvari su manitol, natrij kroskarmeloza i magnezijev stearat. Navedene formulacije korištene su za izradu minitableta promjera 3 mm. Provedena je karakterizacija minitableta ispitivanjem ujednačenosti masa tableta, raspadljivosti tableta, i ispitivanjem sadržaja djelatne tvari u tabletama te profila otpuštanja djelatne tvari.

Abstract (english)

Within this study, orally disintegrated mini-tablets with Lurasidone hydrochloride drug were prepared. It is characterized by poor solubility and thus low drug bioavailability. Solubility is attempted to increase by preparation of solid dispersion using lyophilization or freeze-drying, whereby the drug is attempted to be embedd in a hydrophilic polymer matrix of polyethylene glycol 4000. Three samples with different ratios of drug and excipient were treated by lyophilization. Derived lyophilisates were characterized by moisture content, differential scanning calorimetry, X-ray powder diffraction and infrared spectroscopy. Four drug formulations were prepared using process technologies of lyophilization, granulation and tabletting. Three drug formulations were prepared with lyophilisates of Lurasidone hydrochloride and polyethylene glycol, and using granulate of excipients, while the fourth formulation was prepared by granulation of drug and excipients in fluidized bed by in situ melting. Excipients used were mannitol, sodium croscarmellose and magnesium stearate. Mentioned formulations were used to produce mini-tablets of 3 mm in diameter. Characterization of mini-tablets is carried out by testing the tablet mass uniformity, tablet disintegration, and by studying the drug content in tablets and drug release profiles.

• Keywords: raspadljiva minitableta za usta; poboljšanje topljivosti lijeka; liofilizacija; raspadljivost tableta; otpuštanje djelatne tvari
• Keywords (english): orally disintegrated mini-tablet; drug solubility enhancement; lyophilization; tablet disintegration; drug release
• Language: croatian
• URN:NBN: urn:nbn:hr:149:347383
• 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: 2020-11-03 09:50:29