Mimicking the dynamic Colonic microbiota in vitro to gain a better understanding on the in vivo metabolism of xenobiotics: Degradation of sulfasalazine

Beeck, Regine; Glöckl, Gunnar; Krause, Julius; Schick, Philipp

doi:10.1016/j.ijpharm.2021.120704

Cited by 7 publications

(10 citation statements)

References 31 publications

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“…Despite the advantages of this system, it does not consider the dynamic environment in terms of nutrient availability from the digestion process and ascending colon simulation, where drug release should ideally be initiated. Very recently, a new system (Mimicol) was introduced which attempts to address the dynamic nature of the human colon by simulating more dynamic and physiologically relevant conditions (Figure 7) [142]. In this system, the medium (Chaedler broth) is inoculated with a sample complex microbiota pool derived from a fecal sample cultivation for 24 h. The medium is changed over time to allow continuous bacterial growth, and redox potential and pH are continuously monitored.…”

Section: In Vitro Methodologies For Enzymatic-triggered Drug-release ...mentioning

confidence: 99%

“…The system also includes a mixing element design to simulate the peristalsis in the colon and the volume is kept at 150 mL. The dynamic ascending colon conditions simulated with the Mimicol system resulted in twofold increase in sulfasalazine degradation in comparison with a static batch fermenter [142].…”

Section: In Vitro Methodologies For Enzymatic-triggered Drug-release ...mentioning

confidence: 99%

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In Vitro Methodologies for Evaluating Colon-Targeted Pharmaceutical Products and Industry Perspectives for Their Applications

et al. 2022

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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.

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Section: In Vitro Methodologies For Enzymatic-triggered Drug-release ...mentioning

confidence: 99%

Section: In Vitro Methodologies For Enzymatic-triggered Drug-release ...mentioning

confidence: 99%

In Vitro Methodologies for Evaluating Colon-Targeted Pharmaceutical Products and Industry Perspectives for Their Applications

et al. 2022

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“…The current solutions are overly complex. We have successfully addressed this with the MimiCol bioreactor [ 14 ]. However, the reactor had to be developed further to facilitate replication.…”

Section: Discussionmentioning

confidence: 99%

“…The experimental conditions are based on those of the MimiCol [ 14 ] and displayed in Table 1 . Bacteria are cultivated at a temperature of 37 °C under anaerobic conditions, which are generated via headspace gassing of the vessels with nitrogen.…”

Section: Methodsmentioning

confidence: 99%

“…What all these models have in common is the complexity of their design and that it is time consuming to acquire enough data to show statistical significance [ 12 , 13 ]. Our first approach in the development of an in vitro model representing the dynamic conditions in the ascending colon was the MimiCol [ 14 ]. In brief, the model can simulate bacterial composition and dynamic pH levels in an anaerobic atmosphere mixed by slow moving perpendicular blades.…”

Section: Introductionmentioning

confidence: 99%

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An Advanced Bioreactor Simulating Dynamic Physiological Conditions in the Human Ascending Colon: MimiCol3

et al. 2022

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In recent years, the colon has become a hot topic in biopharmaceutical research as several in vitro models of the human colon have been presented. A major focus is on the characterization of the microbiota and its capabilities. The aim of the present study was to further develop the MimiCol, preserving its properties and accelerating data acquisition. Emphasis was placed on the simplicity of its design and easy scalability. To prove the viability of the concept, degradation of sulfasalazine was investigated, and the bacterial composition during the experiment was assessed by 16S rRNA sequencing. The transfer of the experimental conditions to the new model was successful. Commercially available components were implemented in the setup. The model MimiCol3 represented the colon ascendens satisfactorily in its properties regarding volume, pH value, and redox potential. 16S rRNA sequencing led to further insights into the bacterial composition in the vessels. Degradation of sulfasalazine was in good agreement with in vivo data. The new model of the colon ascendens MimiCol3 enabled us to collect more reliable data, as three experiments were conducted simultaneously under the same conditions.

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Influence of enzymatic modification on the structure, antioxidant activity, and prebiotic activity of ginseng neutral polysaccharide

Dong,

Hou,

Zheng

et al. 2025

International Journal of Biological Macromolecules

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Mimicking the dynamic Colonic microbiota in vitro to gain a better understanding on the in vivo metabolism of xenobiotics: Degradation of sulfasalazine

Cited by 7 publications

References 31 publications

In Vitro Methodologies for Evaluating Colon-Targeted Pharmaceutical Products and Industry Perspectives for Their Applications

In Vitro Methodologies for Evaluating Colon-Targeted Pharmaceutical Products and Industry Perspectives for Their Applications

An Advanced Bioreactor Simulating Dynamic Physiological Conditions in the Human Ascending Colon: MimiCol3

Influence of enzymatic modification on the structure, antioxidant activity, and prebiotic activity of ginseng neutral polysaccharide

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