Primjena liofilizacije i granuliranja u povećanju topljivosti djelatne tvari

master's thesis

• Title (english): Applying lyophilisation and granulation for drug solubility enhancement
• Author: Valentino Subotičanec
• 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: 2020-09-18, Croatia
• Scientific / art field, discipline and subdiscipline: TECHNICAL SCIENCES; Chemical Engineering

Abstract

Lurasidon-hidroklorid je djelatna tvar izrazito male topljivosti u vodenom mediju što otežava njegovu primjenu u liječenju psihičkih poremećaja. S ciljem povećanja njegove topljivosti pripravljeni su granulati djelatne tvari i čvrste disperzije djelatne tvari u matrici hidrofilnog polimera, poli(etilen-glikol) (PEG) procesom liofilizacije. Dobivene čvrste disperzije karakterizirane su diferencijalnom pretražnom kalorimetrijom, rendgenskom difrakcijskom analizom praha i infracrvenom spektroskopijom. Testirana je prividna topljivost djelatne tvari u čvrstim disperzijama. U pripravi raspadljivih tableta promjera 8 mm korišteni su liofilizati i granulirane mješavine s ugrađenom djelatnom tvari. Korišteni su manitol, natrijeva kroskarmeloza te mikrokristalna celuloza kao pomoćne tvari. Karakterizacija raspadljivih tableta uključivala je ispitivanje ujednačenosti masa te testiranje njihove raspadljivosti. Vrijeme raspadljivosti za sve tablete manje je od 3 minute. Profili oslobađanja ukazuju na brže oslobađanje djelatne tvari iz raspadljivih tableta pripravljenih iz čvrstih disperzija u odnosu na one koje sadrže čisti netretirani lurasidon-hidroklorid (LRS HCl) i one s granuliranom mješavinom djelatne tvari i polimera. Testirana je primjenjivost modela u opisu profila oslobađaja lurasidon-hidroklorida.

Abstract (english)

Lurasidone hydrochloride is an active substance of extremely low solubility in an aqueous medium, which makes it difficult to use in the treatment od mental disorders. In order to increase its solubility, granules of the active substrance and solid dispersions of drug in a hydrophilic polymer matrix, poly (ethylene glycol) (PEG) were prepared by the lyophilization process. Obtained solid dispersions were characterized by differential screening calorimetry, X-ray powder difractionanalysis and infrared spectoscopy. The apparent solubility of drug was tested in solid dispersions. Lyophilisates and granulated mixtures with incoporated active substance were used in the preparation of disintegrating tablets with 8 mm in diameter. Mannitol, croscarmellose sodium and microcrystalline cellulose were used as excipients. Characterization of disintegrating tablets involved testing the mass uniforimity and its disintegration. The disintegration time for all tablets is less than 3 minutes. Release profiles indicate faster drug release from disintegrating tablets prepared from solid dispersions in comparison to those containing pure untreated lurasidone hydrochloride (LRS HCl) and those with granulated mixture of drug and polymer. The applicability of models was tested to describe release profiles for lurasidone hydrochloride.

• Keywords: lurasidon-hidroklorid; poboljšanje topljivosti lijeka; čvrsta disperzija; liofilizacija; granuliranje; raspadljiva tableta za usta; oslobađanje djelatne tvari
• Keywords (english): lurasidone hydrochloride; drug solubility improvement; solid dispersion; lyophilization; granulation; orally disintegrating tablet; drug release
• Language: croatian
• URN:NBN: urn:nbn:hr:149:099463
• Study programme: Title: Environmental Engineering - Graduate study; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra inženjer/inženjerka ekoinženjerstva (magistar/magistra inženjer/inženjerka ekoinženjerstva)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2022-04-13 13:46:28