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Kristalizacija je jedan od najviše korištenih procesa dobivanja i pročišćavanja djelatne tvari u farmaceutskoj industriji. Najčešće se provodi kristalizacija iz otopine. Kod provođenja procesa kristalizacije potrebno je odabrati prikladna otapala, odrediti topljivost djelatne tvari, raspon temperature u kojem se proces provodi i način postizanja prezasićenosti. Svi navedeni faktori utječu na granulometrijska svojstva kristala te eventualnu pojavu polimorfizma. Kao pomoć u podešavanju uvjeta procesa kristalizacije i drugih inženjerskih procesa koriste se razni programi koji olakšavaju odabir potrebnih procesnih uvjeta za dobivanje željenih rezultata. U općem dijelu rada prikazan je pregled načina provođenja kristalizacije i važnih čimbenika koji utječu na nju, načini karakterizacije kristala te upotreba programa Dynochem. U radu je prikazano određivanje topljivosti djelatne tvari te usporedba rezultata dobivenih uz pomoć Dynochem-a. Provedena je kristalizacija hlađenjem pri čemu je ispitan utjecaj sustava otapala na granulometrijska svojstva nastalih kristala te njihovu unutarnju strukturu. Osim toga, provedena su preliminarna istraživanja za provedbu sferične kristalizacije. Uz pomoć programa Dynochem odabran je sustav od tri otapala (otapalo, antiotapalo i otapalo za premoštenje) koji se smatraju pogodnima za provedbu sferične kristalizacije. Nakon karakterizacije dobivenih kristala može se zaključiti da je sustav aceton-voda pogodniji za rad od sustava etanol-voda zato što se iz sustava s acetonom dobivaju krupniji kristali pogodniji za daljnju upotrebu u istraživanju. Iako su za odabrani sustav otapala i sastave unutar heterogenog područja provedeni eksperimenti sferične kristalizacije, kristali nisu dobiveni. Može se pretpostaviti da je potrebno, osim termodinamičkih uvjeta, podesiti i kinetičke parametre procesa. Crystallization is one of the most used processes for obtaining and purifying active pharmaceutical ingredients (APIs) in the pharmaceutical industry. Crystallization from solution is most often carried out. When carrying out the crystallization process, it is necessary to choose suitable solvents, determine the solubility of the API, the temperature range in which the process is carried out and the method of achieving supersaturation. All the mentioned factors affect the granulometric properties of the crystal and the eventual occurrence of polymorphism. As an aid in adjusting the conditions of the crystallization process and other engineering processes, various programs are used to speed up the selection of the necessary process conditions in order to obtain the desired results. In this paper, an overview of crystallization methods and important factors that affect it, methods of crystal characterization and the use of the Dynochem program is presented. The paper presents the determination of the solubility of the API and the comparison of the results obtained using Dynochem. Crystallization by cooling was performed, during which the effect of the solvent system on the granulometric properties of the resulting crystals and their internal structure was examined. In addition, preliminary research was conducted for the implementation of spherical crystallization. Using Dynochem program, a system of three solvents (solvent, antisolvent and bridging solvent) was selected, which are considered suitable for carrying out spherical crystallization. After the characterization of the obtained crystals, it can be concluded that the acetone-water system is more suitable to work with than the ethanol-water system because larger crystals are obtained from the acetone system, which are more suitable for further use in research. Although spherical crystallization experiments were performed for the selected solvent system and compositions within the heterogeneous region, no crystals were obtained. It can be assumed that, in addition to thermodynamic conditions, it is necessary to adjust the kinetic parameters of the process. |
