caa a22 4500 44531267X CHVBK 20180317142635.0 cr unu---uuuuu 170323e20111201xx s 000 0 eng 10.1007/s11095-011-0496-4 doi (NATIONALLICENCE)springer-10.1007/s11095-011-0496-4 Effect of Cryogrinding on Chemical Stability of the Sparingly Water-Soluble Drug Furosemide [Elektronische Daten] [Karolina Adrjanowicz, Kamil Kaminski, Katarzyna Grzybowska, Lukasz Hawelek, Marian Paluch, Irena Gruszka, Daniel Zakowiecki, Wieslaw Sawicki, Przemyslaw Lepek, Wojciech Kamysz, Lukasz Guzik] ABSTRACT: Purpose: To investigate the effect of cryogrinding on chemical stability of the diuretic agent furosemide and its mixtures with selected excipients. Methods: Furosemide was ground at liquid nitrogen temperature for 30, 60, 120 and 180min. Mixtures of furosemide-PVP and furosemide-inulin (1:1) were milled under cryogenic conditions. Materials were analyzed by XRD, UPLC, MS and NMR. Results: Upon increasing the milling time, a significant build-up of an unidentified impurity 1, probably the main degradation product, was noticed. Cogrinding of furosemide with PVP and inulin worsened chemical stabilization of the pharmaceutical. The main degradation product formed upon cryomilling was subsequently identified as 4-chloro-5-sulfamoylanthranilic acid (CSA). Based on some theoretical considerations involving specific milling conditions, the milling intensity and an expected specific milling dose have been calculated. Results indicate that cryogenic grinding is capable to initiate mechanically induced decomposition of furosemide. Conclusions: Cryogenic grinding can activate and accelerate not only structural changes (solid state amorphization) but also chemical decomposition of pharmaceuticals. A cryogenic milling device should be considered as a chemical reactor, where under favourable conditions chemical reactions could be mechanically initiated. The Author(s), 2011 amorphous pharmaceuticals nationallicence cryogenic grinding nationallicence furosemide nationallicence mechnochemical reactions nationallicence solid state amorphization nationallicence Adrjanowicz Karolina Department of Biophysics and Molecular Physics, Institute of Physics, University of Silesia, ul. Uniwersytecka 4, 40-007, Katowice, Poland aut Kaminski Kamil Department of Biophysics and Molecular Physics, Institute of Physics, University of Silesia, ul. Uniwersytecka 4, 40-007, Katowice, Poland aut Grzybowska Katarzyna Department of Biophysics and Molecular Physics, Institute of Physics, University of Silesia, ul. Uniwersytecka 4, 40-007, Katowice, Poland aut Hawelek Lukasz Department of Biophysics and Molecular Physics, Institute of Physics, University of Silesia, ul. Uniwersytecka 4, 40-007, Katowice, Poland aut Paluch Marian Department of Biophysics and Molecular Physics, Institute of Physics, University of Silesia, ul. Uniwersytecka 4, 40-007, Katowice, Poland aut Gruszka Irena Department of Experimental Physics, Institute of Physics, University of Silesia, ul. Uniwersytecka 4, 40-007, Katowice, Poland aut Zakowiecki Daniel Preformulation Department R&D, Pharmaceutical Works Polpharma SA, Pelplinska 19, 83-200, Starogard Gdanski, Poland aut Sawicki Wieslaw Department of Physical Chemistry, Medical University of Gdansk, Hallera 107, 80-416, Gdansk, Poland aut Lepek Przemyslaw Department of Physical Chemistry, Medical University of Gdansk, Hallera 107, 80-416, Gdansk, Poland aut Kamysz Wojciech Department of Inorganic Chemistry, Medical University of Gdansk, Hallera 107, 80-416, Gdansk, Poland aut Guzik Lukasz Department of Inorganic Chemistry, Medical University of Gdansk, Hallera 107, 80-416, Gdansk, Poland aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/12(2011-12-01), 3220-3236 0724-8741 28:12<3220 2011 28 11095 https://doi.org/10.1007/s11095-011-0496-4 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-011-0496-4 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Adrjanowicz Karolina Department of Biophysics and Molecular Physics, Institute of Physics, University of Silesia, ul. Uniwersytecka 4, 40-007, Katowice, Poland aut NATIONALLICENCE 700 1- Kaminski Kamil Department of Biophysics and Molecular Physics, Institute of Physics, University of Silesia, ul. Uniwersytecka 4, 40-007, Katowice, Poland aut NATIONALLICENCE 700 1- Grzybowska Katarzyna Department of Biophysics and Molecular Physics, Institute of Physics, University of Silesia, ul. Uniwersytecka 4, 40-007, Katowice, Poland aut NATIONALLICENCE 700 1- Hawelek Lukasz Department of Biophysics and Molecular Physics, Institute of Physics, University of Silesia, ul. Uniwersytecka 4, 40-007, Katowice, Poland aut NATIONALLICENCE 700 1- Paluch Marian Department of Biophysics and Molecular Physics, Institute of Physics, University of Silesia, ul. Uniwersytecka 4, 40-007, Katowice, Poland aut NATIONALLICENCE 700 1- Gruszka Irena Department of Experimental Physics, Institute of Physics, University of Silesia, ul. Uniwersytecka 4, 40-007, Katowice, Poland aut NATIONALLICENCE 700 1- Zakowiecki Daniel Preformulation Department R&D, Pharmaceutical Works Polpharma SA, Pelplinska 19, 83-200, Starogard Gdanski, Poland aut NATIONALLICENCE 700 1- Sawicki Wieslaw Department of Physical Chemistry, Medical University of Gdansk, Hallera 107, 80-416, Gdansk, Poland aut NATIONALLICENCE 700 1- Lepek Przemyslaw Department of Physical Chemistry, Medical University of Gdansk, Hallera 107, 80-416, Gdansk, Poland aut NATIONALLICENCE 700 1- Kamysz Wojciech Department of Inorganic Chemistry, Medical University of Gdansk, Hallera 107, 80-416, Gdansk, Poland aut NATIONALLICENCE 700 1- Guzik Lukasz Department of Inorganic Chemistry, Medical University of Gdansk, Hallera 107, 80-416, Gdansk, Poland aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/12(2011-12-01), 3220-3236 0724-8741 28:12<3220 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer