Formation of Ciprofloxacin–Isonicotinic Acid Cocrystal Using Mechanochemical Synthesis Routes—An Investigation into Critical Process Parameters
The mechanochemical synthesis of cocrystals has been introduced as a promising approach of formulating poorly water-soluble active pharmaceutical ingredients (APIs). In this study, hot-melt extrusion (HME) as a continuous process and grinding and ball milling as batch processes were employed to expl...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-03-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/3/634 |
| _version_ | 1797443570099027968 |
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| author | Maryam Karimi-Jafari Ahmad Ziaee Emmet O’Reilly Denise Croker Gavin Walker |
| author_facet | Maryam Karimi-Jafari Ahmad Ziaee Emmet O’Reilly Denise Croker Gavin Walker |
| author_sort | Maryam Karimi-Jafari |
| collection | DOAJ |
| description | The mechanochemical synthesis of cocrystals has been introduced as a promising approach of formulating poorly water-soluble active pharmaceutical ingredients (APIs). In this study, hot-melt extrusion (HME) as a continuous process and grinding and ball milling as batch processes were employed to explore the feasibility of cocrystallization. Ciprofloxacin (CIP) and isonicotinic acid (INCA) were selected as the model API and coformer. CIP–INCA cocrystal was produced in all techniques. It was revealed that higher cocrystal content could be achieved at longer durations of grinding and ball milling. However, milling for more than 10 min led to increased co-amorphous content instead of cocrystal. A design of experiment (DoE) approach was used for deciphering the complex correlation of screw configuration, screw speed, and temperature as HME process parameters and their respective effect on final relative cocrystal yield. Statistical analysis showed that screw configuration, temperature, and their interaction were the most critical factors affecting cocrystallization. Interestingly, screw speed had minimal impact on the relative cocrystallization yield. Cocrystallization led to increased dissolution rate of CIP in phosphate buffer up to 2.5-fold. Overall, this study shed a light on the potential of mechanochemical synthesis techniques with special focus on HME as a continuous process for producing cocrystals. |
| first_indexed | 2024-03-09T12:58:00Z |
| format | Article |
| id | doaj.art-8ead843badc14d3eb7014a660d3c2270 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T12:58:00Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-8ead843badc14d3eb7014a660d3c22702023-11-30T21:57:44ZengMDPI AGPharmaceutics1999-49232022-03-0114363410.3390/pharmaceutics14030634Formation of Ciprofloxacin–Isonicotinic Acid Cocrystal Using Mechanochemical Synthesis Routes—An Investigation into Critical Process ParametersMaryam Karimi-Jafari0Ahmad Ziaee1Emmet O’Reilly2Denise Croker3Gavin Walker4Synthesis & Solid State Pharmaceutical Centre (SSPC), Department of Chemical Sciences, Bernal Institute, University of Limerick, V94 T9PX Limerick, IrelandSynthesis & Solid State Pharmaceutical Centre (SSPC), Department of Chemical Sciences, Bernal Institute, University of Limerick, V94 T9PX Limerick, IrelandSynthesis & Solid State Pharmaceutical Centre (SSPC), Department of Chemical Sciences, Bernal Institute, University of Limerick, V94 T9PX Limerick, IrelandSynthesis & Solid State Pharmaceutical Centre (SSPC), Department of Chemical Sciences, Bernal Institute, University of Limerick, V94 T9PX Limerick, IrelandSynthesis & Solid State Pharmaceutical Centre (SSPC), Department of Chemical Sciences, Bernal Institute, University of Limerick, V94 T9PX Limerick, IrelandThe mechanochemical synthesis of cocrystals has been introduced as a promising approach of formulating poorly water-soluble active pharmaceutical ingredients (APIs). In this study, hot-melt extrusion (HME) as a continuous process and grinding and ball milling as batch processes were employed to explore the feasibility of cocrystallization. Ciprofloxacin (CIP) and isonicotinic acid (INCA) were selected as the model API and coformer. CIP–INCA cocrystal was produced in all techniques. It was revealed that higher cocrystal content could be achieved at longer durations of grinding and ball milling. However, milling for more than 10 min led to increased co-amorphous content instead of cocrystal. A design of experiment (DoE) approach was used for deciphering the complex correlation of screw configuration, screw speed, and temperature as HME process parameters and their respective effect on final relative cocrystal yield. Statistical analysis showed that screw configuration, temperature, and their interaction were the most critical factors affecting cocrystallization. Interestingly, screw speed had minimal impact on the relative cocrystallization yield. Cocrystallization led to increased dissolution rate of CIP in phosphate buffer up to 2.5-fold. Overall, this study shed a light on the potential of mechanochemical synthesis techniques with special focus on HME as a continuous process for producing cocrystals.https://www.mdpi.com/1999-4923/14/3/634cocrystalmechanochemical synthesishot-melt extrusionball millinggrindingsolid state chemistry |
| spellingShingle | Maryam Karimi-Jafari Ahmad Ziaee Emmet O’Reilly Denise Croker Gavin Walker Formation of Ciprofloxacin–Isonicotinic Acid Cocrystal Using Mechanochemical Synthesis Routes—An Investigation into Critical Process Parameters Pharmaceutics cocrystal mechanochemical synthesis hot-melt extrusion ball milling grinding solid state chemistry |
| title | Formation of Ciprofloxacin–Isonicotinic Acid Cocrystal Using Mechanochemical Synthesis Routes—An Investigation into Critical Process Parameters |
| title_full | Formation of Ciprofloxacin–Isonicotinic Acid Cocrystal Using Mechanochemical Synthesis Routes—An Investigation into Critical Process Parameters |
| title_fullStr | Formation of Ciprofloxacin–Isonicotinic Acid Cocrystal Using Mechanochemical Synthesis Routes—An Investigation into Critical Process Parameters |
| title_full_unstemmed | Formation of Ciprofloxacin–Isonicotinic Acid Cocrystal Using Mechanochemical Synthesis Routes—An Investigation into Critical Process Parameters |
| title_short | Formation of Ciprofloxacin–Isonicotinic Acid Cocrystal Using Mechanochemical Synthesis Routes—An Investigation into Critical Process Parameters |
| title_sort | formation of ciprofloxacin isonicotinic acid cocrystal using mechanochemical synthesis routes an investigation into critical process parameters |
| topic | cocrystal mechanochemical synthesis hot-melt extrusion ball milling grinding solid state chemistry |
| url | https://www.mdpi.com/1999-4923/14/3/634 |
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