In Vitro Methodologies for Evaluating Colon-Targeted Pharmaceutical Products and Industry Perspectives for Their Applications
Several locally acting colon-targeted products to treat colonic diseases have been recently developed and marketed, taking advantage of gastrointestinal physiology to target delivery. Main mechanisms involve pH-dependent, time-controlled and/or enzymatic-triggered release. With site of action locate...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-01-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/2/291 |
| _version_ | 1797477248474808320 |
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| author | Mauricio A. García Felipe Varum Jozef Al-Gousous Michael Hofmann Susanne Page Peter Langguth |
| author_facet | Mauricio A. García Felipe Varum Jozef Al-Gousous Michael Hofmann Susanne Page Peter Langguth |
| author_sort | Mauricio A. García |
| collection | DOAJ |
| description | Several locally acting colon-targeted products to treat colonic diseases have been recently developed and marketed, taking advantage of gastrointestinal physiology to target delivery. Main mechanisms involve pH-dependent, time-controlled and/or enzymatic-triggered release. With site of action located before systemic circulation and troublesome colonic sampling, there is room for the introduction of meaningful in vitro methods for development, quality control (QC) and regulatory applications of these formulations. A one-size-fits-all method seems unrealistic, as the selection of experimental conditions should resemble the physiological features exploited to trigger the release. This article reviews the state of the art for bio-predictive dissolution testing of colon-targeted products. Compendial methods overlook physiological aspects, such as buffer molarity and fluid composition. These are critical for pH-dependent products and time-controlled systems containing ionizable drugs. Moreover, meaningful methods for enzymatic-triggered products including either bacteria or enzymes are completely ignored by pharmacopeias. Bio-predictive testing may accelerate the development of successful products, although this may require complex methodologies. However, for high-throughput routine testing (e.g., QC), simplified methods can be used where balance is struck between simplicity, robustness and transferability on one side and bio-predictivity on the other. Ultimately, bio-predictive methods can occupy a special niche in terms of supplementing plasma concentration data for regulatory approval. |
| first_indexed | 2024-03-09T21:14:53Z |
| format | Article |
| id | doaj.art-4f8499e8a1104f68b689f5d4cecb8533 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T21:14:53Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-4f8499e8a1104f68b689f5d4cecb85332023-11-23T21:36:49ZengMDPI AGPharmaceutics1999-49232022-01-0114229110.3390/pharmaceutics14020291In Vitro Methodologies for Evaluating Colon-Targeted Pharmaceutical Products and Industry Perspectives for Their ApplicationsMauricio A. García0Felipe Varum1Jozef Al-Gousous2Michael Hofmann3Susanne Page4Peter Langguth5Department of Biopharmaceutics and Pharmaceutical Technology, Johannes Gutenberg University Mainz, 55099 Mainz, GermanyPharmaceutical Research and Development, F. Hoffmann-La Roche Ltd., 4070 Basel, SwitzerlandDepartment of Biopharmaceutics and Pharmaceutical Technology, Johannes Gutenberg University Mainz, 55099 Mainz, GermanyPharmaceutical Research and Development, F. Hoffmann-La Roche Ltd., 4070 Basel, SwitzerlandPharmaceutical Research and Development, F. Hoffmann-La Roche Ltd., 4070 Basel, SwitzerlandDepartment of Biopharmaceutics and Pharmaceutical Technology, Johannes Gutenberg University Mainz, 55099 Mainz, GermanySeveral locally acting colon-targeted products to treat colonic diseases have been recently developed and marketed, taking advantage of gastrointestinal physiology to target delivery. Main mechanisms involve pH-dependent, time-controlled and/or enzymatic-triggered release. With site of action located before systemic circulation and troublesome colonic sampling, there is room for the introduction of meaningful in vitro methods for development, quality control (QC) and regulatory applications of these formulations. A one-size-fits-all method seems unrealistic, as the selection of experimental conditions should resemble the physiological features exploited to trigger the release. This article reviews the state of the art for bio-predictive dissolution testing of colon-targeted products. Compendial methods overlook physiological aspects, such as buffer molarity and fluid composition. These are critical for pH-dependent products and time-controlled systems containing ionizable drugs. Moreover, meaningful methods for enzymatic-triggered products including either bacteria or enzymes are completely ignored by pharmacopeias. Bio-predictive testing may accelerate the development of successful products, although this may require complex methodologies. However, for high-throughput routine testing (e.g., QC), simplified methods can be used where balance is struck between simplicity, robustness and transferability on one side and bio-predictivity on the other. Ultimately, bio-predictive methods can occupy a special niche in terms of supplementing plasma concentration data for regulatory approval.https://www.mdpi.com/1999-4923/14/2/291colon targetingmodified drug releasepH-dependent releaseenzymatic triggered releasebio-relevant dissolutionquality control |
| spellingShingle | Mauricio A. García Felipe Varum Jozef Al-Gousous Michael Hofmann Susanne Page Peter Langguth In Vitro Methodologies for Evaluating Colon-Targeted Pharmaceutical Products and Industry Perspectives for Their Applications Pharmaceutics colon targeting modified drug release pH-dependent release enzymatic triggered release bio-relevant dissolution quality control |
| title | In Vitro Methodologies for Evaluating Colon-Targeted Pharmaceutical Products and Industry Perspectives for Their Applications |
| title_full | In Vitro Methodologies for Evaluating Colon-Targeted Pharmaceutical Products and Industry Perspectives for Their Applications |
| title_fullStr | In Vitro Methodologies for Evaluating Colon-Targeted Pharmaceutical Products and Industry Perspectives for Their Applications |
| title_full_unstemmed | In Vitro Methodologies for Evaluating Colon-Targeted Pharmaceutical Products and Industry Perspectives for Their Applications |
| title_short | In Vitro Methodologies for Evaluating Colon-Targeted Pharmaceutical Products and Industry Perspectives for Their Applications |
| title_sort | in vitro methodologies for evaluating colon targeted pharmaceutical products and industry perspectives for their applications |
| topic | colon targeting modified drug release pH-dependent release enzymatic triggered release bio-relevant dissolution quality control |
| url | https://www.mdpi.com/1999-4923/14/2/291 |
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