Preparation of new doxycycline monohydrate polymorphs by ultrasonication enhanced supercritical antisolvent recrystallization process
Polymorphism is a crucial factor in the pharmaceutical industry, as different polymorphs can display different physicochemical properties, including stability, solubility, and/or bioavailability. The ultrasonication-enhanced supercritical antisolvent recrystallization (UE-SAR) process is a novel inv...
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Elsevier
2025-06-01
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| Series: | Journal of CO2 Utilization |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2212982025000666 |
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| author | Snehashis Nandi Miguel A. Rodrigues Andreia Duarte Teresa G. Nunes Luis Padrela |
| author_facet | Snehashis Nandi Miguel A. Rodrigues Andreia Duarte Teresa G. Nunes Luis Padrela |
| author_sort | Snehashis Nandi |
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| description | Polymorphism is a crucial factor in the pharmaceutical industry, as different polymorphs can display different physicochemical properties, including stability, solubility, and/or bioavailability. The ultrasonication-enhanced supercritical antisolvent recrystallization (UE-SAR) process is a novel investigated approach for producing novel polymorphs.This work aimed to generate and characterize doxycycline monohydrate (DOXY·H2O forms II, III, and IV) polymorphs produced from suspensions of its as received form (DOXY·H2O form I) using the UE-SAR process. A two-stage Design of Experiments (DoE) analysis was performed to assess the impact of various processing parameters such as ultrasonication, pressure, temperature, and residence time on the polymorphic outcome in each experimental run. The solid state characterization revealed that the produced polymorphs (DOXY·H2O form II, DOXY·H2O form III) have distinct powder X-ray diffraction (PXRD), Raman, Fourier Transform Infrared (FTIR) patterns and higher thermal stability. Moreover, the structures of DOXY·H2O forms I and II were further elucidated by solid state nuclear magnetic resonance (SS NMR) from 13 C and 15 N cross polarization (CP) and magic angle spinning (MAS) spectra. Overall, the results from this work highlight that use US-SAR method can induce the formation of different supramolecular structures in tetracyclines when they are suspended in a supercritical phase, and polymorphic purity can be enhanced by prolonged ultrasonication. |
| format | Article |
| id | doaj-art-1d50f85d08b84dae853d876753c0872d |
| institution | Kabale University |
| issn | 2212-9839 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of CO2 Utilization |
| spelling | doaj-art-1d50f85d08b84dae853d876753c0872d2025-08-20T03:49:32ZengElsevierJournal of CO2 Utilization2212-98392025-06-019610308210.1016/j.jcou.2025.103082Preparation of new doxycycline monohydrate polymorphs by ultrasonication enhanced supercritical antisolvent recrystallization processSnehashis Nandi0Miguel A. Rodrigues1Andreia Duarte2Teresa G. Nunes3Luis Padrela4Department of Chemical Sciences, Bernal Institute, University of Limerick, Limerick V94 T9PX, Ireland; SSPC, The Research Ireland Centre for Pharmaceuticals, Bernal Institute, University of Limerick, V94 T9PX, IrelandCentro de Química Estrutural and Department of Chemical Engineering, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, Lisboa 1049-001, PortugalCentro de Química Estrutural and Department of Chemical Engineering, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, Lisboa 1049-001, PortugalCentro de Química Estrutural and Department of Chemical Engineering, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, Lisboa 1049-001, PortugalDepartment of Chemical Sciences, Bernal Institute, University of Limerick, Limerick V94 T9PX, Ireland; SSPC, The Research Ireland Centre for Pharmaceuticals, Bernal Institute, University of Limerick, V94 T9PX, Ireland; Corresponding author at: Department of Chemical Sciences, Bernal Institute, University of Limerick, Limerick V94 T9PX, Ireland.Polymorphism is a crucial factor in the pharmaceutical industry, as different polymorphs can display different physicochemical properties, including stability, solubility, and/or bioavailability. The ultrasonication-enhanced supercritical antisolvent recrystallization (UE-SAR) process is a novel investigated approach for producing novel polymorphs.This work aimed to generate and characterize doxycycline monohydrate (DOXY·H2O forms II, III, and IV) polymorphs produced from suspensions of its as received form (DOXY·H2O form I) using the UE-SAR process. A two-stage Design of Experiments (DoE) analysis was performed to assess the impact of various processing parameters such as ultrasonication, pressure, temperature, and residence time on the polymorphic outcome in each experimental run. The solid state characterization revealed that the produced polymorphs (DOXY·H2O form II, DOXY·H2O form III) have distinct powder X-ray diffraction (PXRD), Raman, Fourier Transform Infrared (FTIR) patterns and higher thermal stability. Moreover, the structures of DOXY·H2O forms I and II were further elucidated by solid state nuclear magnetic resonance (SS NMR) from 13 C and 15 N cross polarization (CP) and magic angle spinning (MAS) spectra. Overall, the results from this work highlight that use US-SAR method can induce the formation of different supramolecular structures in tetracyclines when they are suspended in a supercritical phase, and polymorphic purity can be enhanced by prolonged ultrasonication.http://www.sciencedirect.com/science/article/pii/S2212982025000666Doxycycline monohydrateUltrasonicationUE-SARDoEPolymorphismThermal stability |
| spellingShingle | Snehashis Nandi Miguel A. Rodrigues Andreia Duarte Teresa G. Nunes Luis Padrela Preparation of new doxycycline monohydrate polymorphs by ultrasonication enhanced supercritical antisolvent recrystallization process Journal of CO2 Utilization Doxycycline monohydrate Ultrasonication UE-SAR DoE Polymorphism Thermal stability |
| title | Preparation of new doxycycline monohydrate polymorphs by ultrasonication enhanced supercritical antisolvent recrystallization process |
| title_full | Preparation of new doxycycline monohydrate polymorphs by ultrasonication enhanced supercritical antisolvent recrystallization process |
| title_fullStr | Preparation of new doxycycline monohydrate polymorphs by ultrasonication enhanced supercritical antisolvent recrystallization process |
| title_full_unstemmed | Preparation of new doxycycline monohydrate polymorphs by ultrasonication enhanced supercritical antisolvent recrystallization process |
| title_short | Preparation of new doxycycline monohydrate polymorphs by ultrasonication enhanced supercritical antisolvent recrystallization process |
| title_sort | preparation of new doxycycline monohydrate polymorphs by ultrasonication enhanced supercritical antisolvent recrystallization process |
| topic | Doxycycline monohydrate Ultrasonication UE-SAR DoE Polymorphism Thermal stability |
| url | http://www.sciencedirect.com/science/article/pii/S2212982025000666 |
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