Naslov
Crystallization of a Pharmaceutical Co-crystal by Advanced Supersaturation Control

Autori
Šahnić, Damir ; Kišiček, Dejan ; Dorić, Hrvoje ; Mohler, Ivan ; Bolf, Nenad

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

Izvornik
26. Hrvatski skup kemičara i kemijskih inženjera / Galić, Nives ; Rogošić, Marko - Zagreb : Hrvatsko društvo kemijskih inženjera i tehnologa (HDKI), 2019, 187-187

Skup
26. hrvatski skup kemičara i kemijskih inženjera (26HSKIKI) ; 4. simpozij Vladimir Prelog

Mjesto i datum
Šibenik, Hrvatska, 09.04.2019. - 12.04.2019

Vrsta sudjelovanja
Poster

Vrsta recenzije
Recenziran

Ključne riječi
crystalization, process monitoring, process control, supersaturation control, ATR-UV/Vis spectroscopy, PLRS

Sažetak
In situ monitoring and control of crystallization processes is receiving more and more interest in the pharmaceutical and specialty chemicals industries over the past decade [1]. Physical characteristics of APIs such as the polymorphic form, morphology and particle size distribution which are important for subsequent downstream processing are determined by the crystallization process. By manipulating the supersaturation level as the driving force for crystallization, different outcomes with respect to the aforementioned characteristics can be achieved. To that end, robust control strategies of crystallization processes using supersaturation control, achieved by the combined use of Process Analytical Technologies (PATs) and chemometrics can be developed and applied to obtain the desired physical characteristics of APIs [2]. The development of a quantitative in-line ATR- UV/Vis spectroscopic method for solute concentration monitoring during a crystallization process of an API co-crystal is described. The method is comprised of a chemometric PLSR calibration model used for solute concentration calculation from acquired spectra and actual temperatures. The use of this method together with the reactor temperature control achieved by applying feedback supersaturation control (C-control) during the course of a seeded cooling crystallization experiment is also described. Data acquisition for the model development, data preprocessing, model building and C-control was performed with the aid of a proprietary, in-house developed software suite, CrystCal. The developed method proved to be a robust and fast way to monitor the solute concentration in-situ, thereby enabling the C-control system to cool the crystallization mixture while keeping the supersaturation at a desired level. The developed system can be used for other target supersaturation levels and has potential for application on other crystallization systems.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Kemijsko inženjerstvo

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