Stability of Ternary Drug–Drug–Drug Coamorphous Systems Obtained Through Mechanochemistry
<b>Background/Objectives:</b> This study investigates the preparation of coamorphous systems composed entirely of active pharmaceutical ingredients (APIs), namely praziquantel, niclosamide, and mebendazole. The objective was to formulate and characterize binary and ternary coamorphous sy...
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2025-01-01
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| author | Ilenia D’Abbrunzo Elisabetta Venier Francesca Selmin Irena Škorić Enrico Bernardo Giuseppe Procida Beatrice Perissutti |
| author_facet | Ilenia D’Abbrunzo Elisabetta Venier Francesca Selmin Irena Škorić Enrico Bernardo Giuseppe Procida Beatrice Perissutti |
| author_sort | Ilenia D’Abbrunzo |
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| description | <b>Background/Objectives:</b> This study investigates the preparation of coamorphous systems composed entirely of active pharmaceutical ingredients (APIs), namely praziquantel, niclosamide, and mebendazole. The objective was to formulate and characterize binary and ternary coamorphous systems to evaluate their structural, thermal, and stability properties. <b>Methods:</b> Ten different mixtures (binary and ternary) were designed through a mixture design approach and prepared using a sustainable, one-step neat grinding process in a lab-scale vibrational mill. The systems were prepared reproducibly within 4 h across the entire experimental domain. Structural characterization was performed using PXRD and FTIR to confirm the absence of crystalline domains and the presence of molecular interactions. The glass transition temperature (T<sub>g</sub>) was theoretically calculated using the Gordon–Taylor equation for three-component systems and determined experimentally via DSC. Stability studies were conducted on seven systems under different storage conditions (−30 °C, 5 °C, 25 °C, and 40 °C) for six months. <b>Results:</b> PXRD analysis confirmed the formation of coamorphous systems with no crystalline phases. DSC revealed a single T<sub>g</sub> for most systems, indicating homogeneity. Stability studies demonstrated that five out of seven systems adhered to the “T<sub>g</sub>—50 °C” stability rule, remaining physically stable over six months. Recrystallization studies indicated diverse pathways: some systems reverted to their original crystalline phases, while others formed new entities such as cocrystals. <b>Conclusions:</b> This study highlights the feasibility of coamorphous systems composed of multiple APIs using a simple, solvent-free grinding approach. The findings underscore the importance of molecular interactions in determining stability and recrystallization behavior, offering insights for designing robust coamorphous formulations. |
| format | Article |
| id | doaj-art-b82c11e04d114ff090c2ab897ec6f1ec |
| institution | Kabale University |
| issn | 1999-4923 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj-art-b82c11e04d114ff090c2ab897ec6f1ec2025-01-24T13:45:55ZengMDPI AGPharmaceutics1999-49232025-01-011719210.3390/pharmaceutics17010092Stability of Ternary Drug–Drug–Drug Coamorphous Systems Obtained Through MechanochemistryIlenia D’Abbrunzo0Elisabetta Venier1Francesca Selmin2Irena Škorić3Enrico Bernardo4Giuseppe Procida5Beatrice Perissutti6Department of Chemical and Pharmaceutical Sciences, University of Trieste, Piazzale Europa 1, 34127 Trieste, ItalyDepartment of Chemical and Pharmaceutical Sciences, University of Trieste, Piazzale Europa 1, 34127 Trieste, ItalyDepartment of Pharmaceutical Sciences, University of Milan, Via G. Colombo, 71, 20133 Milan, ItalyDepartment of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Marulićev trg 19, 10000 Zagreb, CroatiaDepartment of Industrial Engineering, University of Padova, Via F. Marzolo 9, 35131 Padova, ItalyDepartment of Chemical and Pharmaceutical Sciences, University of Trieste, Piazzale Europa 1, 34127 Trieste, ItalyDepartment of Chemical and Pharmaceutical Sciences, University of Trieste, Piazzale Europa 1, 34127 Trieste, Italy<b>Background/Objectives:</b> This study investigates the preparation of coamorphous systems composed entirely of active pharmaceutical ingredients (APIs), namely praziquantel, niclosamide, and mebendazole. The objective was to formulate and characterize binary and ternary coamorphous systems to evaluate their structural, thermal, and stability properties. <b>Methods:</b> Ten different mixtures (binary and ternary) were designed through a mixture design approach and prepared using a sustainable, one-step neat grinding process in a lab-scale vibrational mill. The systems were prepared reproducibly within 4 h across the entire experimental domain. Structural characterization was performed using PXRD and FTIR to confirm the absence of crystalline domains and the presence of molecular interactions. The glass transition temperature (T<sub>g</sub>) was theoretically calculated using the Gordon–Taylor equation for three-component systems and determined experimentally via DSC. Stability studies were conducted on seven systems under different storage conditions (−30 °C, 5 °C, 25 °C, and 40 °C) for six months. <b>Results:</b> PXRD analysis confirmed the formation of coamorphous systems with no crystalline phases. DSC revealed a single T<sub>g</sub> for most systems, indicating homogeneity. Stability studies demonstrated that five out of seven systems adhered to the “T<sub>g</sub>—50 °C” stability rule, remaining physically stable over six months. Recrystallization studies indicated diverse pathways: some systems reverted to their original crystalline phases, while others formed new entities such as cocrystals. <b>Conclusions:</b> This study highlights the feasibility of coamorphous systems composed of multiple APIs using a simple, solvent-free grinding approach. The findings underscore the importance of molecular interactions in determining stability and recrystallization behavior, offering insights for designing robust coamorphous formulations.https://www.mdpi.com/1999-4923/17/1/92ternary coamorphousbinary coamorphousdrug-to-drug-to-drug coamorphousglass transitionphysical stabilitystorage temperature |
| spellingShingle | Ilenia D’Abbrunzo Elisabetta Venier Francesca Selmin Irena Škorić Enrico Bernardo Giuseppe Procida Beatrice Perissutti Stability of Ternary Drug–Drug–Drug Coamorphous Systems Obtained Through Mechanochemistry Pharmaceutics ternary coamorphous binary coamorphous drug-to-drug-to-drug coamorphous glass transition physical stability storage temperature |
| title | Stability of Ternary Drug–Drug–Drug Coamorphous Systems Obtained Through Mechanochemistry |
| title_full | Stability of Ternary Drug–Drug–Drug Coamorphous Systems Obtained Through Mechanochemistry |
| title_fullStr | Stability of Ternary Drug–Drug–Drug Coamorphous Systems Obtained Through Mechanochemistry |
| title_full_unstemmed | Stability of Ternary Drug–Drug–Drug Coamorphous Systems Obtained Through Mechanochemistry |
| title_short | Stability of Ternary Drug–Drug–Drug Coamorphous Systems Obtained Through Mechanochemistry |
| title_sort | stability of ternary drug drug drug coamorphous systems obtained through mechanochemistry |
| topic | ternary coamorphous binary coamorphous drug-to-drug-to-drug coamorphous glass transition physical stability storage temperature |
| url | https://www.mdpi.com/1999-4923/17/1/92 |
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