Razvoj i optimizacija procesa sušenja aktivne farmaceutske supstance u sušioniku s raspršivanjem

doctoral thesis

• Title (english): Development and optimization of spray drying process for drying of a pharmaceutical ingredient
• Author: Igor Nežić
• Mentor: Aleksandra Sander (mentor)
• Mentor: Ernest Meštrović (mentor)
• Committee member: Jasna Prlić Kardum (predsjednik povjerenstva)
• Committee member: Mirela Leskovac (član povjerenstva)
• Committee member: Tomislav Penović (član povjerenstva)
• Granter: University of Zagreb; Faculty of Chemical Engineering and Technology; Zagreb
• Defense date and country: 2018-04-27, Croatia
• Scientific / art field, discipline and subdiscipline: TECHNICAL SCIENCES; Chemical Engineering; Mechanical, Thermal and Separation Processes
• Universal decimal classification (UDC): 66 - Chemical technology. Chemical and related industries

Abstract

Sušenje raspršivanjem, među ostalim tehnologijama i činjenicom da se radi o kontinuiranom proizvodnom procesu, vrlo je korisno za proizvodnju amorfnih krutih materijala. To je uglavnom zbog mogućnosti brzog isparavanja otapala što dovodi do brze pretvorbe otopine u čvrsto stanje. Pored kinetike isparavanja, postoje različiti procesni parametri koji utječu na fizikalna i kemijska svojstva tako dobivenog materijala. U ovom radu ispitivana je mogućnost dobivanja stabilne amorfne strukture aktivnog farmaceutskog sastojka, kao i stabilne čvrste disperzije s polimerom u sušioniku s raspršivanjem. Uzimajući u obzir topljivost svih sastojaka, njihovu kristalizacijsku i kemijsku stabilnost, utjecaj materijala konstrukcije na njihovu stabilnost, izabran je optimalni sustav za sušenje raspršivanjem. Otopina hidroklorida aktivne farmaceutske supstance u smjesi vode i acetonitrila sušena je na različitim temperaturama, konfiguracijama mlaznica i brzinama protoka dušika korištenog za atomizaciju, kao i brzinama protoka otopine. Analizirani su utjecaji procesnih uvjeta na svojstva dobivenog proizvoda. Dobiveni proizvodi karakterizirani su i identificirani nizom analitičkih i fizikalnih metoda. Rezultati su pokazali da se sušenjem raspršivanjem dobiva stabilna amorfna struktura aktivnog farmaceutskog sastojka visoke kemijske čistoće te su definirani optimalni uvjeti procesa. Amorfna struktura je stabilna pri temperaturama ispod 200 °C, a iznad prelazi u novu kristalnu strukturu. Čvrsta disperzija pokazala je poboljšanu stabilnost u usporedbi s čistim amorfnim aktivnim sastojkom. Uvjeti visoke relativne vlažnosti zraka dovode do djelomične transformacije iz amorfne u kristalnu strukturu. Uvećanje procesa sušenja otopine aktivnog farmaceutskog sastojka iz laboratorijskog sušionika Buchi 290 u industrijsko mjerilo, istraživano je na uređaju Anhydro 53 PSD CC. Dobiveni rezultati pokazuju da su najsličniji uvjeti sušenja ostvareni kada su u Buchiu upotrijebljeni veći promjeri mlaznice, a u Anhydro uređaju kombinacija više temperature sušenja s nižim tlakom na mlaznici ili nižom temperaturom sušenja uz veći tlak. Čak ni kod najvišeg protoka dušika na mlaznici, u Anhydru nisu ostvareni slični uvjeti sušenja dobivenih u laboratorijskom mjerilu korištenjem manjih promjera mlaznice.

Abstract (english)

Spray drying, amongst other technologies and fact that it is a continuous manufacturing process, is a very useful method for manufacturing of amorphous solid materials. This is mainly due to the possibility of fast solvent evaporation that leads to a rapid transformation of solution to a solid state. Besides evaporation kinetics, there are various process parameters that influence physical and chemical characteristics of such obtained material. In this work, the possibility of obtaining a stable amorphous structure of the active pharmaceutical ingredient as well as stable solid dispersion with a polymer in a spray-dryer was examined. Taking into account solubility of all ingredients, their crystalization and chemical stability, influence of material of construction on their stability, optimal system for spray drying process was chosen. A solution of the hydrochloride crystalline structure of the active pharmaceutical ingredient in a mixture of water and acetonitrile was dried at different temperatures, nozzle configurations and flow rates of nitrogen used for atomization, as well as the flow rates of the solution. The influence of the process conditions on the properties of the product was analyzed. The final dried products were characterized and identified with a variety of analytical and physical methods. The results showed that a stable amorphous structure of the high purity active pharmaceutical ingredient is obtained with a spray drying, and that the optimal conditions of the process are defined. The amorphous structure is stable at temperatures below 200 °C when it is transformed into a new crystal structure. Solid dispersion showed improved stability compared to pure amorphous active ingredient. Conditions of high relative air humidity lead to partial transformation. Spray drying of the solution of the active pharmaceutical ingredient from the laboratory drier Buchi 290 to pilot drier 53 PSD CC Anhydro was investigated. Obtained results show that the most similar drying conditions were achieved when larger nozzle diameters were used in Buchi, and in Anhydro a combination of higher drying temperature with lower nozzle pressure, or lower drying temperature with higher pressure. Even the highest nozzle pressures in Anhydro could not produce similar drying conditions as obtained in laboratory scale by the use of smaller nozzle diameters.

• Keywords: amorfna struktura; čvrsta disperzija; sušenje raspršivanjem; uvećanje procesa; vilazodon hidroklorid
• Keywords (english): amorphous form; solid dispersion; spray drying; scale-up; vilazodone hydrochloride
• Language: croatian
• URN:NBN: urn:nbn:hr:149:478015
• Promotion: 2018
• Study programme: Title: Chemical Engineering - Doctoral Course; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje tehničkih znanosti, polje kemijsko inženjerstvo (doktor/doktorica znanosti, područje tehničkih znanosti, polje kemijsko inženjerstvo)
• Type of resource: Text
• Extent: 176 str. ; 30 cm
• File origin: Born digital
• Access conditions: Open access
• Created on: 2023-08-30 11:42:04