Razvoj procesa kristalizacije za djelatnu tvar

master's thesis

• Title (english): Crystallization process development of an active pharmaceutical ingredient
• Author: Lana Topalović
• Mentor: Jasna Prlić Kardum (mentor)
• Committee member: Jasna Prlić Kardum (predsjednik povjerenstva)
• Committee member: Aleksandra Sander (član povjerenstva)
• Committee member: Tomislav Penović (član povjerenstva)
• Granter: University of Zagreb; Faculty of Chemical Engineering and Technology; Zagreb
• Defense date and country: 2021-06-29, Croatia
• Scientific / art field, discipline and subdiscipline: TECHNICAL SCIENCES; Chemical Engineering

Abstract

Kristalizacija ima široku primjenu u farmaceutskoj i kemijskoj industriji kao jedna od najjednostavnijih i najjeftinijih metoda dobivanja čvrstih tvari visoke čistoće. Način provedbe kristalizacije te uvjeti pri kojima se kristalizacija provodi uvelike utječu na konačna svojstva kristala kao što su oblik i forma kristala, čistoća, raspodjela veličina čestica i dr. Kokristali su od značajnog interesa u farmaceutskoj industriji jer omogućuju promjenu fizikalno - kemijskih svojstava djelatne tvari (eng. Active pharmaceutical ingredient, API) bez mijenjanja njihove molekulske strukture,. U ovom radu istraživan je proces kristalizacije kokristala tosilatne soli djelatne tvari s bademnom kiselinom te je optimiran proces šaržne kristalizacije. Određen je utjecaj dodatka cjepiva te hidrodinamičkih uvjeta na kemijsku i polimorfnu čistoću kristala, raspodjelu veličina čestica i iskorištenje procesa. U radu je praćen oblik kristala pretražnim elektronskim mikroskopom, a metodom laserske difrakcije određena je raspodjela veličina čestica. Također je praćena i linijska raspodjela veličina čestica primjenom sonde za mjerenje refleksije usredotočene zrake. Kristalna forma dobivenih kokristala tosilatne soli djelatne tvari određivana je pomoću rendgenske difrakcije praha. Na temelju svih dobivenih rezultata odabrani su optimalni procesni uvjeti kristalizacije istraživanog API-a.

Abstract (english)

Crystallization is widely used in the pharmaceutical and chemical industries as one of the simplest and cheapest method of obtaining high purity solids. The method of crystallization and the conditions under which crystallization is carried out greatly affect the final properties of the crystal, such as the shape and form of the crystal, purity, particle size distribution, etc. Cocrystals are crystalline material of significant interest in the pharmaceutical industry, allowing to change the physico-chemical properties of the active substance (API) without changing their molecular structures. In this paper, the process of crystallization of cocrystals of the tosylate salt of the active substance with mandelic acid was investigated and the batch crystallization process was optimized. The influence of the additional set of hydrodynamic conditions on the chemical and polymorphic purity of crystals, particle size distribution and process efficiency was determined. The shape of the crystal was monitored by a scanning electron microscope and a particle size distribution was determined by laser diffraction. Linear particle size distribution was also monitored using a focused beam reflection probe. The crystalline form of the obtained cocrystals of the tosylate salt of the active substance was determined by powder X-ray diffraction. Based on all the obtained results, the most optimal API crystallization process was selected.

• Keywords: kristalizacija; djelatna tvar; kokristal; cjepivo; raspodjela veličina čestica; kristalna forma
• Keywords (english): crystallization; active pharmaceutical ingredient; cocrystal; seed; particle size distribution; crystalline form
• Language: croatian
• URN:NBN: urn:nbn:hr:149:663902
• Study programme: Title: Materials Science and 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: Closed access
• Created on: 2023-04-05 13:44:47