Šaržna kristalizacija fosamprenavir-kalcija

master's thesis

• Title (english): Batch crystallization of fosamprenavir calcium
• Author: Valentina Šimatović
• Mentor: Jasna Prlić Kardum (mentor)
• Committee member: Jasna Prlić Kardum (predsjednik povjerenstva)
• Committee member: Nenad Bolf (član povjerenstva)
• Committee member: Mirela Leskovac (član povjerenstva)
• Granter: University of Zagreb; Faculty of Chemical Engineering and Technology; Zagreb
• Defense date and country: 2021-09-23, Croatia
• Scientific / art field, discipline and subdiscipline: TECHNICAL SCIENCES; Chemical Engineering

Abstract

Većina postupaka farmaceutske proizvodnje uključuje niz procesa kristalizacije kako bi se dobio produkt željenih svojstava. Radni uvjeti procesa kristalizacije određuju fizikalna svojstva proizvoda, poput čistoće, oblika i raspodjele veličine kristala. Nakon pretraživanja sustava i odabira pogodnog otapala i antiotapala provedena je šaržna kristalizacija fosampranavir kalcija uz dodatak antiotapala vode pri temperaturi 25°C i 30°C. U radu je ispitan utjecaj dodatka različitog volumnog udjela antiotapala na granulometrijska svojstava kristala fosamprenavir kalcija. Fosamprenavir kalcij se koristi kao predlijek amprenavira u borbi protiv virusa humane imunodeficijencije. Utvrđeno je da povećanjem volumnog udjela antiotapala dolazi do smanjenja koncentracije otopine, koncentracija postiže vrlo niske vrijednosti na oko 30% udjela vode, iz čega bi se moglo zaključiti da je došlo do izdvajanja većine soli iz otopine. Na temelju slika dobivenih svjetlosnim mikroskopom, te rapodijele veličine kristala snimljene rendgenskom difrakcijom ustanovljen porast udjela sitnijih kristala s porastom volumnog udjela antiotapala. Također, pokazano je da su kristali dobiveni u eksperimentima provedenim na višoj temperaturi (30°C) krupniji, a udio sitnijih čestica (u području oko 1 μm) je znatno manji. Kinetičke konstante: konstanta brzine rasta kristala kg i red rasta kristala g određene su potencijskom jednadžbom, a prisutnost polimorfnih formi u uzorcima utvrđena je analizom DSC-krivulja dobivenih tehnikom diferencijalne pretražne kalorimetrije (DSC).

Abstract (english)

Most pharmaceutical manufacturing processes include a series of crystallization processes to obtain the product of the desired properties. The operating conditions of the crystallization process determine the physical properties of the products such as the crystal purity, shape, and size distribution. After the search and selection of suitable solvent and anti-solvent, batch crystallization of fosamprenavir calcium was performed with the addition of water at
25 ° C and 30 ° C. The effect of the addition of a different volume fraction of antisolvents on the granulometric properties of fosamprenavir calcium crystals was investigated. Fosamprenavir calcium is used as a prodrug of amprenavir in the fight against human immunodeficiency virus. It was found that increasing the volume fraction of anti-solvent leads to a decrease in the concentration of the solution, the concentration reaches very low values at about 30% water content, from which it could be concluded that most of the salts were separated from the solution. Based on the images obtained by light microscopy and the crystal size distribution determinated using laser disfraction method, an increase in the proportion of smaller crystals with an increase in the volume fraction of antisolvents was established. Also, it was shown that the crystals obtained in the experiments at a higher temperature (30 ° C) were larger, and the proportion of smaller particles (in the range of about 1 μm) was significantly smaller. Kinetic constants: the crystal growth rate constant kg and the crystal growth order g were determined by the potential equation, and the presence of polymorphic forms in the samples was determined by analysis of DSC-curves obtained by differential scanning calorimetry (DSC).

• Keywords: kristalizacija uz dodatak antiotapala; fosamprenavir kalcij; granulometrijska svojstva kristala; kinetičke konstante
• Keywords (english): antisolvent crystalization; fosamprenavir calcium; granulometric properties; kinetic constants
• Language: croatian
• URN:NBN: urn:nbn:hr:149:446478
• Project: Number: KK.01.1.1.07.0017; Title: Napredno vođenje procesa kristalizacije; Title: Advanced Control of Crystallization Process; Acronym: CrystAPC; Leader: Nenad Bolf; Jurisdiction: Croatia; Funder: EK; Funding stream: EFRR
• 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: 2023-04-14 12:48:09