{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T03:28:50Z","timestamp":1785209330611,"version":"3.55.0"},"reference-count":47,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2020,7,9]],"date-time":"2020-07-09T00:00:00Z","timestamp":1594252800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union through the European Social Fund under the Operational Programme Knowledge Education Development 2014\u20132020","award":["project POWR.03.02.00-00-I026\/17-00"],"award-info":[{"award-number":["project POWR.03.02.00-00-I026\/17-00"]}]},{"name":"Ministry of Science and Higher Education, Poland","award":["grants No 02-0015\/07\/505 and 0912\/SBAD\/0903"],"award-info":[{"award-number":["grants No 02-0015\/07\/505 and 0912\/SBAD\/0903"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>The low water solubility of benzodiazepines seriously affects their bioavailability and, in consequence, their biological activity. Since co-crystallization has been found to be a promising way to modify undesirable properties in active pharmaceutical ingredients, the objective of this study was to prepare co-crystals of two benzodiazepines, chlordiazepoxide and lorazepam. Using different co-crystallization procedures, slurry evaporation and liquid-assisted grinding, co-crystals of chlordiazepoxide with p-aminobenzoic acid and lorazepam with nicotinamide were prepared for the first time. Confirmation that co-crystals were obtained was achieved through a comparison of the data acquired for both co-crystals using differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), Fourier-transform infrared (FTIR) and Raman spectroscopy, with comparisons acquired for the physical mixtures of both benzodiazepines and coformers. The compatibility of PXRD patterns of both benzodiazepines co-crystals with those contained in the base Powder Diffraction File (PDF-4+) suggests that new crystal structures were indeed created under the co-crystallization procedure. Single-crystal X-ray diffraction revealed that a chlordiazepoxide co-crystal with p-aminobenzoic acid and a lorazepam co-crystal with nicotinamide crystallized in the monoclinic P21\/n and P21\/c space group, respectively, with one molecule of benzodiazepine and one of coformer in the asymmetric unit. FTIR and Raman spectroscopy corroborated that benzodiazepine and coformer are linked by a hydrogen bond without proton exchange. Furthermore, a DSC study revealed that single endothermic DSC peaks assigned to the melting of co-crystals differ slightly depending on the co-crystallization procedures and solvent used, as well as differing from those of starting components.<\/jats:p>","DOI":"10.3390\/pharmaceutics12070648","type":"journal-article","created":{"date-parts":[[2020,7,10]],"date-time":"2020-07-10T09:45:31Z","timestamp":1594374331000},"page":"648","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Structural Characterization of Co-Crystals of Chlordiazepoxide with p-Aminobenzoic Acid and Lorazepam with Nicotinamide by DSC, X-ray Diffraction, FTIR and Raman Spectroscopy"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7632-9564","authenticated-orcid":false,"given":"Patrycja","family":"Garbacz","sequence":"first","affiliation":[{"name":"Department of Analytical Chemistry, Faculty of Pharmacy, Medical University of Gdansk, Gen. J. Hallera 107, 80-416 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8243-7035","authenticated-orcid":false,"given":"Dominik","family":"Paukszta","sequence":"additional","affiliation":[{"name":"Institute of Chemical Technology and Engineering, Poznan University of Technology, Berdychowo 4, 60-695 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4559-7870","authenticated-orcid":false,"given":"Artur","family":"Sikorski","sequence":"additional","affiliation":[{"name":"Department of Physical Chemistry, Faculty of Chemistry, University of Gdansk, Wita Stwosza 63, 80-308 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3577-1377","authenticated-orcid":false,"given":"Marek","family":"Wesolowski","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry, Faculty of Pharmacy, Medical University of Gdansk, Gen. 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