Naslov projekta
Razvoj i primjena in-line metode Ramanove spektroskopije u istraživanju
lijekova
Development and application of an in-line method of Raman spectroscopy
for drug research**
Voditelj: Dr. sc. Predrag Novak, red. prof.
Institucija partner: PLIVA HRVATSKA d.o.o.
Partner institution: PLIVA CROATIA Ltd.
Financiranje/Funding
Nacionalna zaklada za znanost, visoko školstvo i tehnološki razvoj Republike Hrvatske
Suradnici/Coworkers:
Ernest Meštrović
Zlatko Meić
Tomislav Biljan
Tomica Hrenar
Snežana Miljanić
Ana Kwokal
Dijana Škalec Šamec
Andreja Kišić
Sažetak
Suvremeno istraživanje lijekova danas je nezamislivo bez uporabe sofisticiranih i učinkovitih analitičkih metoda i tehnika. Regulatorne agencije propisuju vrlo stroga pravila za praćenje procesai kontrolu kvalitete u proizvodnji lijekova. Uključivanje Ramanove spektroskopije u regulativu potaknulo je njezinu brzu i široku primjenu u farmaceutskoj industriji kako u fazi istraživanja tako i u samom industrijskom pogonu.
Ciljevi ovog istraživanja stoga su usmjereni prema razvoju i primjeni metode Ramanove spektroskopije kao procesne analitičke metode in-line za monitoring i kontrolu kemijskih i fizičkih procesa bioaktivnih molekula i lijekova. To je izuzetno važno u suvremenom istraživanju i razvoju lijekova jer je s jedne strane za bolju učinkovitost procesa i kontrolu kvalitete proizvoda potrebno razvijati nove pristupe a s druge strane regulatorne agencije propisuju procesne analitičke metode kao metode izbora za monitoring procesa.
U ovome istraživanju primijenit će se Ramanova spketroskopija in-line na modelni sustav koji čini lijek entakapone. Naime, ovaj spoj ima više različitih kristalnih oblika od kojih su neki, zbog svojih fizikalno-kemijskih svojstava od veće farmakološke važnosti pa će biti od izuzetnog značaja da se proces njihovog nastanka može kontrolirati i usmjeriti prema željenom cilju. Očekuje se da će se ovako razvijena metoda moći dalje koristiti u kontroli i proizvodnji drugih lijekova.
Projekt ima stratešku važnost jer obuhvaća područje biomedicine i istraživanja lijekova te novih pristupa u razvitku procesa i proizvoda.
Abstract
The use of sophisticated, advanced and efficient analytical methods and techniques is of the outmost importance in modern drug discovery. Regulatory agencies impose stringent rules and protocols for process monitoring and quality control in pharmaceutical industry. As a part of the regulations Raman spectroscopy has found a widespread use not only in the research and development phase but also in the production process.
In this project a real-time /in situ/ Raman spectroscopy will be used to study Entacapone, an catechol-O-methyl transferase inhibitor used in the treatment of Parkinson's disease as a model system. The Raman sensor as the most appropriate for this system coupled with chemometrics will provide a wealth of information regarding chemical reaction, crystallization and different solid forms. A special attention will be paid to crystal size distribution as one of the main properties that affect therapeutic efficacy. The method will be further validated on similar systems.
In general, the aim of this investigation is therefore directed toward development and application of an in-line Raman spectroscopy technique as a process analytical method for monitoring chemical and physical processes in drug research. This is important because new approaches and methodologies are needed for a better quality control and higher product efficiency on one hand, and the fact that regulatory bodies demand the
use of in-line methods as the methods of choice for process monitoring on the other hand.
The proposed project is completely in-line with the strategic aims and priorities of NZZ because it connects basic research and applications and encourages collaboration and partnerships between academic institution and industry. It includes fields of biomedicine and drug discovery as well as new approaches in process and product developments. Furthermore, natural science and biotechnology are major factors that govern modern drug research in the worldwide pharmaceutical industry contributing to a successfull treatment of various diseases and also to development of knowledge-based technologies.
Scientists and experts of high competence are included into the investigations regarding the proposed project. They are well recognized in the domestic academic community as well as abroad. Considering that the modern Croatian community has important duty to educate experts and scientists, especially the young ones, highly competent for an economic development, this project also aims toward the knowledge transfer between the scientific organization and the partner company. This will undoubtedly contribute to a better understanding and development of scientific competence for demands of the economy.