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Projects / Programmes source: ARRS

NQR - nondestructive method for studying of polymorphism in heteregeneous pharmaceutical systems

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Research activity

Code Science Field Subfield
7.00.00  Interdisciplinary research     

Code Science Field
P260  Natural sciences and mathematics  Condensed matter: electronic structure, electrical, magnetic and optical properties, supraconductors, magnetic resonance, relaxation, spectroscopy 
B740  Biomedical sciences  Pharmacological sciences, pharmacognosy, pharmacy, toxicology 
Keywords
nuclear quadrupole resonance - NQR, polarization enhanced nitrogen NQR, polymorphism, heteregeneous pharmaceutical systems
Evaluation (rules)
source: COBISS
Citations Citations for bibliographic records in COBIB.SI that are linked to records in citation databases
source: WoS source: Scopus source: COBISS
Researchers (19)
no. Code Name and surname Research area Role Period No. of publications
1.  15490  PhD Pegi Ahlin Grabnar  Natural sciences and mathematics  Researcher  2007 - 2010  191 
2.  07518  PhD Tomaž Apih  Natural sciences and mathematics  Researcher  2007 - 2010  264 
3.  15104  PhD Saša Baumgartner  Natural sciences and mathematics  Researcher  2007 - 2010  306 
4.  00004  PhD Robert Blinc  Natural sciences and mathematics  Researcher  2007 - 2010  1,501 
5.  22658  PhD Mateja Cegnar  Natural sciences and mathematics  Researcher  2007 - 2009  91 
6.  29887  PhD Mirjam Gosenca Matjaž  Natural sciences and mathematics  Researcher  2008 - 2010  122 
7.  18272  PhD Alan Gregorovič  Natural sciences and mathematics  Researcher  2009 - 2010  99 
8.  12628  PhD Rok Hren  Engineering sciences and technologies  Researcher  2007 - 2010  226 
9.  08274  PhD Vojko Jazbinšek  Natural sciences and mathematics  Researcher  2007 - 2010  199 
10.  01115  PhD Gojmir Lahajnar  Natural sciences and mathematics  Researcher  2007 - 2009  356 
11.  04317  PhD Janko Lužnik  Natural sciences and mathematics  Researcher  2007 - 2010  223 
12.  02558  PhD Janez Pirnat  Natural sciences and mathematics  Researcher  2007 - 2010  226 
13.  01117  PhD Janez Seliger  Natural sciences and mathematics  Researcher  2007 - 2009  340 
14.  09031  PhD Stanko Srčič  Natural sciences and mathematics  Researcher  2007 - 2010  673 
15.  29888  PhD Rok Šibanc  Natural sciences and mathematics  Researcher  2008 - 2010  62 
16.  28860  PhD Karmen Teskač Plajnšek  Natural sciences and mathematics  Junior researcher  2007 - 2010  50 
17.  00208  PhD Zvonko Trontelj  Natural sciences and mathematics  Principal Researcher  2007 - 2010  595 
18.  11035  PhD Aleksander Zidanšek  Natural sciences and mathematics  Researcher  2007 - 2010  346 
19.  26026  PhD Blaž Zupančič  Natural sciences and mathematics  Junior researcher  2007 - 2010  44 
Organisations (4)
no. Code Research organisation City Registration number No. of publications
1.  0101  Institute of Mathematics, Physics and Mechanics  Ljubljana  5055598000  19,607 
2.  0106  Jožef Stefan Institute  Ljubljana  5051606000  85,680 
3.  0787  University of Ljubljana, Faculty of Pharmacy  Ljubljana  1626973  17,106 
4.  2338  Jožef Stefan International Postgraduate School  Ljubljana  1917544  11,065 
Abstract
Avtorji predlaganega projekta so v večletnem delu z jedrsko kvadrupolno resonanco (JKR) in jedrsko magnetno resonanco (JMR) pokazali, da je mogoče nizko razmerje signal/šum pri JKR 14N zelo izboljšati in izvesti meritev tako hitro, da je s tem odprta pot za marsikatero nadaljevanje. Nekatera so že uspešno izvedli, v tem projektu pa predlagajo raziskave in spremljanje polimorfizma v heterogenih farmacevtskih sistemih. Projekt je multidisciplinaren: v njem združujejo znanje fiziki, farmacevti in kemiki. Predlagane raziskave polimorfizma so pomembne za razumevanje nepričakovanih sprememb biološke aktivnosti učinkovin, a tudi za spremljanje končne faze proizvodnje trdnih heterogenih sistemov in celo za spremljanje fizikalne stabilnosti (v skladišču). Ne nazadnje je celotno poznavanje nastopanja polimorfov pri neki učinkovini lahko kritično pri obvladovanju industrijske lastnine (patenti) in pri pripravi možnih generičnih učinkovin. V predlaganem projektu bomo izvedli študij polimorfizma v nekaterih sulfonamidih s polarizacijsko ojačano JKR 14N. Nadaljevali bomo z raziskavami polimorfizmov v dihidropiridinskih derivatih kalcijevih antagonistov. V končni fazi pa bomo spremljali polimorfizem v vzorcih antiulkusnih in antiinflamatornih učinkovin kot čistih snovi, vgrajenih v heterogene sisteme in v končnih produktih, ki so v embalaži.
Significance for science
The reasearch of new pharmaceutical sample (medicines) requires from the beginning a careful search for possible appearance od polymorphism. We would like to find during the basic research steps with different spectroscopic methods better ways for the detection and identification of polymorphs in medicines. During our research of improvement the s/n ratio in NQR at low frequencies (100 kHz to 5 MHz) we succeded with the prepolarization of protons and with the transfer of polarization to nitrogen nuclei during the process od adiabatic demagnetisation to improve the s/n ratio of 14N NQR signal. The measured drugs need to have suitable relaxation times of protons and nitrogen nuclei. Our application of this technique to study polymorphism in pharmaceutical compounds demonstrate that NQR spectroscopy could become in the near future a good supplemental method to the X-ray diffraction metod in determination of polymorphism in pharmaceutical research and industry . At the same time we search for the alternative detection methods of low frequency NQR signals. We detected successfully low frequency NQR signals by using SQUID sensors as well as by applying the alcaline atomic vapor sensors (we used K atoms). Using the potassium atomic vapor sensor, combined with 2 tunable diode lasers we achieved in the frequency range dc -3,5 MHz about 5 to 10 times higher sensitivity, compared with the classical NQR spectrometer's sensitivity, in detecting low frequency nitrogen signals.
Significance for the country
The Slovene producers of drugs are faced - like all other in the world - with the requirement to determine promptly and with high probability the appearance of polymorphism in new products already during the research steps as well as during the production process (possibly on-line in real time) when the substance entered in the production. Our results, after completed this research project, demonstrate that the suggested radiofrequency 14N NQR spectroscopy fulfil our expectations and is suitable to enter the research labs of drugs producers. During this reserach we also found that the same 14N NQR improved spectroscopy represent a good tool in detecting the counterfeit and badly produced medicines which are comming to Europe from some Assian producers. (We are one out of seven partners in the EU FP-7 project CONPHIRMER, which will start in the year 2011.)
Most important scientific results Annual report 2008, 2009, final report, complete report on dLib.si
Most important socioeconomically and culturally relevant results Annual report 2008, 2009, final report, complete report on dLib.si
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