Dry Amorphization of Itraconazole Using Mesoporous Silica and Twin-Screw Technology
<b>Background/Objectives:</b> Amorphization of an active pharmaceutical ingredient (API) can improve its dissolution and enhance bioavailability. Avoiding solvents for drug amorphization is beneficial due to environmental issues and potential solvent residues in the final product. <b&...
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2024-10-01
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| author | Margarethe Richter Simon Welzmiller Fred Monsuur Annika R. Völp Joachim Quadflieg |
| author_facet | Margarethe Richter Simon Welzmiller Fred Monsuur Annika R. Völp Joachim Quadflieg |
| author_sort | Margarethe Richter |
| collection | DOAJ |
| description | <b>Background/Objectives:</b> Amorphization of an active pharmaceutical ingredient (API) can improve its dissolution and enhance bioavailability. Avoiding solvents for drug amorphization is beneficial due to environmental issues and potential solvent residues in the final product. <b>Methods:</b> Dry amorphization using a twin-screw extruder is presented in this paper. A blend of mesoporous silica particles and crystalline itraconazole was processed using a pharma-grade laboratory scale twin-screw extruder. The influence of different screw configurations and process parameters was tested. Particle size and shape are compared in scanning electron microscopy (SEM) images. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) are used to determine the residual amount of crystalline itraconazole in the final product. <b>Results:</b> An optimized screw configuration for the process was found which leads to more than 90% amorphous API when processed at room temperature. Full amorphization was reached at 70 °C. The specific mechanic energy (<i>SME</i>) introduced into the material during twin-screw processing is crucial for the dry amorphization. The higher the <i>SME</i>, the lower the residual amount of crystalline API. Two months after processing, however, recrystallization was observed by XRD. <b>Conclusions:</b> Dry processing using a twin-screw extruder is continuous, free of solvents and can be performed at low temperatures. This study proves the concept of twin-screw processing with mesoporous silica for dry amorphization of itraconazole. |
| format | Article |
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| institution | DOAJ |
| issn | 1999-4923 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | MDPI AG |
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| series | Pharmaceutics |
| spelling | doaj-art-b51d836f05e74aafac6d38f7e7df3ffc2025-08-20T02:48:02ZengMDPI AGPharmaceutics1999-49232024-10-011611136810.3390/pharmaceutics16111368Dry Amorphization of Itraconazole Using Mesoporous Silica and Twin-Screw TechnologyMargarethe Richter0Simon Welzmiller1Fred Monsuur2Annika R. Völp3Joachim Quadflieg4Thermo Fisher Scientific, Pfannkuchstr. 10-12, 76185 Karlsruhe, GermanyThermo Fisher Scientific, Im Steingrund 4-6, 63303 Dreieich, GermanySil’innov, Rue de Liege 2, 6180 Courcelles, BelgiumThermo Fisher Scientific, Pfannkuchstr. 10-12, 76185 Karlsruhe, GermanyGrace GmbH, In der Hollerhecke 1, 67547 Worms, Germany<b>Background/Objectives:</b> Amorphization of an active pharmaceutical ingredient (API) can improve its dissolution and enhance bioavailability. Avoiding solvents for drug amorphization is beneficial due to environmental issues and potential solvent residues in the final product. <b>Methods:</b> Dry amorphization using a twin-screw extruder is presented in this paper. A blend of mesoporous silica particles and crystalline itraconazole was processed using a pharma-grade laboratory scale twin-screw extruder. The influence of different screw configurations and process parameters was tested. Particle size and shape are compared in scanning electron microscopy (SEM) images. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) are used to determine the residual amount of crystalline itraconazole in the final product. <b>Results:</b> An optimized screw configuration for the process was found which leads to more than 90% amorphous API when processed at room temperature. Full amorphization was reached at 70 °C. The specific mechanic energy (<i>SME</i>) introduced into the material during twin-screw processing is crucial for the dry amorphization. The higher the <i>SME</i>, the lower the residual amount of crystalline API. Two months after processing, however, recrystallization was observed by XRD. <b>Conclusions:</b> Dry processing using a twin-screw extruder is continuous, free of solvents and can be performed at low temperatures. This study proves the concept of twin-screw processing with mesoporous silica for dry amorphization of itraconazole.https://www.mdpi.com/1999-4923/16/11/1368twin-screw granulationtwin-screw extruderAPI amorphizationsolubility enhancementmesoporous silicacontinuous manufacturing |
| spellingShingle | Margarethe Richter Simon Welzmiller Fred Monsuur Annika R. Völp Joachim Quadflieg Dry Amorphization of Itraconazole Using Mesoporous Silica and Twin-Screw Technology Pharmaceutics twin-screw granulation twin-screw extruder API amorphization solubility enhancement mesoporous silica continuous manufacturing |
| title | Dry Amorphization of Itraconazole Using Mesoporous Silica and Twin-Screw Technology |
| title_full | Dry Amorphization of Itraconazole Using Mesoporous Silica and Twin-Screw Technology |
| title_fullStr | Dry Amorphization of Itraconazole Using Mesoporous Silica and Twin-Screw Technology |
| title_full_unstemmed | Dry Amorphization of Itraconazole Using Mesoporous Silica and Twin-Screw Technology |
| title_short | Dry Amorphization of Itraconazole Using Mesoporous Silica and Twin-Screw Technology |
| title_sort | dry amorphization of itraconazole using mesoporous silica and twin screw technology |
| topic | twin-screw granulation twin-screw extruder API amorphization solubility enhancement mesoporous silica continuous manufacturing |
| url | https://www.mdpi.com/1999-4923/16/11/1368 |
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