Naslov
INFLUENCE OF ANTISOLVENT ADDITION ON CRYSTALLIZATION KINETICS AND GRANULOMETRIC PROPERTIES OF FOSANPRENAVIR CALCIUM

Autori
Šimatović, Valentina ; Sacher, Josip ; Prlić Kardum, Jasna

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
27HSKIKI - Book of abstracts / - , 2021, 310-310

Skup
27. hrvatski skup kemičara i kemijskih inženjera (27HSKIKI)

Mjesto i datum
Veli Lošinj, Hrvatska, 05.10.2021. - 08.10.2021

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
crystallization ; HIV ; fosamprenavir calcium ; population balance modeling ; parameter estimation

Sažetak
The focus of the pharmaceutical industry is the research and development of an active pharmaceutical ingredient (API) that can be successfully applied for preparing various drug dosage forms. API are complex organic compounds that tend to agglomerate, oiling out, or form hydrates and/or solvates during crystallization. Therefore, crystallization of the API is the first and critical step that needs to be taken to successfully prepare a drug formulation. By developing a controlled crystallization process, obtaining the desired size distribution, yield, form, and purity of crystals is possible.Crystallization can be carried out by various methods that affect supersaturation which is the main factor in the formation of crystals with defined crystal’s properties. Addition of an antisolvent is potentially the best method to achieve controlled and unimodal crystal size distribution (CSD). The research investigates the antisolvent crystallization of fosamprenavir calcium used as an active ingredient for the treatment of HIV. In preliminary study, the width of the metastable zone same as the dependence of fosamprenavir calcium solubility on the added water content for the selected solvent mixture (80 wt% methanol and 20 wt% ethanol) was defined. At constant antisolvent addition rate, the influence of the initial concentration of the solution and a mass fraction of antisolvent on granulometric properties of obtained crystals were examined. Furthermore, a MatLab based program (CrySiV v.1.1) [2] was used for population balance modeling and subsequent simulation of experiments at 30 °C. Solubility parameters were estimated for a pre- defined solubility model and a simple kinetic model consisting of primary nucleation and crystal growth is proposed. Kinetic parameters were estimated by minimization of the objective function using high resolution finite volume algorithm. The objective function takes into account the differences between simulated and measured values of concentration profile during crystallization and final product CSD in equal proportions.

Izvorni jezik
Engleski

Znanstvena područja
Kemijsko inženjerstvo

POVEZANOST RADA