caa a22 4500 445312688 CHVBK 20180317142635.0 cr unu---uuuuu 170323e20111201xx s 000 0 eng 10.1007/s11095-011-0502-x doi (NATIONALLICENCE)springer-10.1007/s11095-011-0502-x A New Method of Producing Monoclinic Paracetamol Suitable for Direct Compression [Elektronische Daten] [Andrey Ogienko, Elena Boldyreva, Andrey Yu Manakov, Vladimir Boldyrev, Alexander Yunoshev, Anna Ogienko, Svetlana Myz, Alexei Ancharov, Andrey Achkasov, Tatiana Drebushchak] ABSTRACT: Purpose: To develop a technique of obtaining monoclinic polymorph of paracetamol suitable for direct compression without excipients. Methods: Preparation of spongy monoclinic paracetamol was based on quench-cooling of paracetamol solutions in water-acetone mixtures sprayed into a vessel with liquid nitrogen followed by removal of solvents by freeze-drying. X-ray powder diffraction was used to study annealing of quench-cooled solutions in "paracetamol-acetone-water” and "acetone-water” systems and to find optimum conditions for obtaining fine particles of pure monoclinic paracetamol. Samples were characterized by electron microscopy; compression properties were measured. Results: The preparation technique gave fine monoclinic paracetamol powder containing agglomerates (30-200μm) composed of flat particles (linear sizes 1-10μm, the thickness 60-150nm). The spongy sample was suitable for direct compression without excipients, stable on storage, and mechanically robust. Mechanically stable tablets pressed from the spongy sample were better soluble in water than commercially available tablets of paracetamol with excipients. Conclusions: The proposed method gave spongy monoclinic paracetamol samples with improved properties. For inexpensive paracetamol, the method may not yield economic advantage. However, the same method based on freeze-drying solutions in mixed aqueous-organic solvents can be used to prepare new improved forms of other molecular solids for pharmaceutical applications. Springer Science+Business Media, LLC, 2011 direct compression nationallicence freeze-drying nationallicence microparticles nationallicence paracetamol nationallicence polymorphs nationallicence X-ray diffraction nationallicence Ogienko Andrey REC-008 "Molecular Design and Ecologically Safe Technologies”, Novosibirsk State University, ul. Pirogova 2, 630090, Novosibirsk, Russia aut Boldyreva Elena REC-008 "Molecular Design and Ecologically Safe Technologies”, Novosibirsk State University, ul. Pirogova 2, 630090, Novosibirsk, Russia aut Yu Manakov Andrey REC-008 "Molecular Design and Ecologically Safe Technologies”, Novosibirsk State University, ul. Pirogova 2, 630090, Novosibirsk, Russia aut Boldyrev Vladimir REC-008 "Molecular Design and Ecologically Safe Technologies”, Novosibirsk State University, ul. Pirogova 2, 630090, Novosibirsk, Russia aut Yunoshev Alexander REC-008 "Molecular Design and Ecologically Safe Technologies”, Novosibirsk State University, ul. Pirogova 2, 630090, Novosibirsk, Russia aut Ogienko Anna REC-008 "Molecular Design and Ecologically Safe Technologies”, Novosibirsk State University, ul. Pirogova 2, 630090, Novosibirsk, Russia aut Myz Svetlana REC-008 "Molecular Design and Ecologically Safe Technologies”, Novosibirsk State University, ul. Pirogova 2, 630090, Novosibirsk, Russia aut Ancharov Alexei REC-008 "Molecular Design and Ecologically Safe Technologies”, Novosibirsk State University, ul. Pirogova 2, 630090, Novosibirsk, Russia aut Achkasov Andrey REC-008 "Molecular Design and Ecologically Safe Technologies”, Novosibirsk State University, ul. Pirogova 2, 630090, Novosibirsk, Russia aut Drebushchak Tatiana REC-008 "Molecular Design and Ecologically Safe Technologies”, Novosibirsk State University, ul. Pirogova 2, 630090, Novosibirsk, Russia aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/12(2011-12-01), 3116-3127 0724-8741 28:12<3116 2011 28 11095 https://doi.org/10.1007/s11095-011-0502-x text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-011-0502-x text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Ogienko Andrey REC-008 "Molecular Design and Ecologically Safe Technologies”, Novosibirsk State University, ul. Pirogova 2, 630090, Novosibirsk, Russia aut NATIONALLICENCE 700 1- Boldyreva Elena REC-008 "Molecular Design and Ecologically Safe Technologies”, Novosibirsk State University, ul. Pirogova 2, 630090, Novosibirsk, Russia aut NATIONALLICENCE 700 1- Yu Manakov Andrey REC-008 "Molecular Design and Ecologically Safe Technologies”, Novosibirsk State University, ul. Pirogova 2, 630090, Novosibirsk, Russia aut NATIONALLICENCE 700 1- Boldyrev Vladimir REC-008 "Molecular Design and Ecologically Safe Technologies”, Novosibirsk State University, ul. Pirogova 2, 630090, Novosibirsk, Russia aut NATIONALLICENCE 700 1- Yunoshev Alexander REC-008 "Molecular Design and Ecologically Safe Technologies”, Novosibirsk State University, ul. Pirogova 2, 630090, Novosibirsk, Russia aut NATIONALLICENCE 700 1- Ogienko Anna REC-008 "Molecular Design and Ecologically Safe Technologies”, Novosibirsk State University, ul. Pirogova 2, 630090, Novosibirsk, Russia aut NATIONALLICENCE 700 1- Myz Svetlana REC-008 "Molecular Design and Ecologically Safe Technologies”, Novosibirsk State University, ul. Pirogova 2, 630090, Novosibirsk, Russia aut NATIONALLICENCE 700 1- Ancharov Alexei REC-008 "Molecular Design and Ecologically Safe Technologies”, Novosibirsk State University, ul. Pirogova 2, 630090, Novosibirsk, Russia aut NATIONALLICENCE 700 1- Achkasov Andrey REC-008 "Molecular Design and Ecologically Safe Technologies”, Novosibirsk State University, ul. Pirogova 2, 630090, Novosibirsk, Russia aut NATIONALLICENCE 700 1- Drebushchak Tatiana REC-008 "Molecular Design and Ecologically Safe Technologies”, Novosibirsk State University, ul. Pirogova 2, 630090, Novosibirsk, Russia aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/12(2011-12-01), 3116-3127 0724-8741 28:12<3116 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer