Kontrola kristalizacije i analiza svojstava čestica aktivne farmaceutske tvari

master's thesis

• Title (english): Control of crystallization and analysis of the properties of the active pharmaceutical ingredient
• Author: Mirna Filakovac
• Mentor: Aleksandra Sander (mentor)
• Committee member: Aleksandra Sander (predsjednik povjerenstva)
• Committee member: Jasna Prlić Kardum (član povjerenstva)
• Committee member: Igor Dejanović (član povjerenstva)
• Granter: University of Zagreb; Faculty of Chemical Engineering and Technology; Zagreb
• Defense date and country: 2019-07-10, Croatia
• Scientific / art field, discipline and subdiscipline: TECHNICAL SCIENCES; Chemical Engineering

Abstract

Kristalizacija je jedan od najvažnijih procesa u farmaceutskoj industriji jer se većina API-ja nalazi u čvrstom obliku. Odabirom povoljnih procesnih uvjeta može se utjecati na čistoću, veličinu te oblik dobivenih kristala. Oblik i veličina bitni su za formuliranje čvrstih dozirnih oblika lijeka, a morfologija za miješanje i kompaktnost. Budući da API-ji često postoje u različitim polimorfnim oblicima, važno je odrediti termodinamički najstabilniju formu kako bi se izbjegle moguće transformacije. U ovom radu istražena je mogućnost kontrole kristalizacije i dobivanja čestica željenih granulometrijskih svojstava te je u konačnici provedena karakterizacija nastalih prašaka. Najveći naglasak dan je na proces kristalizacije kao najčešćeg procesa za dobivanje čistih API-ja u farmaceutskoj industriji. Kristalizacija je provedena pri različitim profilima brzina hlađenja otopine, uz dodatak pomoćne komponente (antiotapala ili cjepiva) te Ostwaldovo zrenje. Kristalizacija uz kubni profil brzine hlađenja provedena je na pogonskom mjerilu. Cilj je bio povećanje čestica, odnosno dobivanje čestica u veličinskom intervalu od 40-90 μm. Provedena je i analiza svojstava API-ja različitih veličina čestica ispitivanjem stabilnosti, kompresibilnosti i ponašanja praška pod utjecajem smičnog naprezanja.

Abstract (english)

Crystallization is one of the most important processes in pharmaceutical industry because most active pharmaceutical ingredients (API) appear in solid form. Choosing favorable process conditions can affect the purity, size, and shape of the crystals obtained. Shape and size are essential for formulation of solid dosage forms and morphology is for mixing and compacting. Since APIs exist in different polymorphic forms, it is important to determine the thermodynamically most stable form to avoid possible transformations. In this case the possibility of controlling crystallization and obtaining particles of desired granulometric properties was investigated and ultimately the characterization of the resulting powders was carried out. The greatest emphasis is given to the process of crystallization as the most common process for obtaining pure APIs in the pharmaceutical industry. Crystallization was carried out at different cooling rate profiles of the solution, with addition of auxiliary component (antisolvent or vaccine), Ostwald ripening and along with the cubic change of the cooling profile which was carried out on the operating scale. The aim was to increase the particle size, ie to obtain particles at a 40-90 μm interval. Analysis of APIs properties of different particle sizes was also performed by testing the stability, compressibility and behaviour of the powder under the influence of shear stress.

• Keywords: aktivna farmaceutska tvar; filtracija; kontrola kristalizacije; raspodjela veličina kristala
• Keywords (english): active pharmaceutical ingredient; filtration; control of crystallization; particle size distribution
• Language: croatian
• URN:NBN: urn:nbn:hr:149:810374
• 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: 2022-02-17 11:23:00