Projects / Programmes
NQR - nondestructive method for studying of polymorphism in heteregeneous pharmaceutical systems
| 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 |
nuclear quadrupole resonance - NQR, polarization enhanced nitrogen NQR, polymorphism, heteregeneous pharmaceutical systems
Researchers (19)
Organisations (4)
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
