Gastrointestinal diseases and their impact on drug solubility: Ulcerative Colitis

Effinger, Angela; O’Driscoll, Caitriona M.; McAllister, Mark; Fotaki, Nikoletta

doi:10.1016/j.ejps.2020.105458

Cited by 6 publications

(5 citation statements)

References 57 publications

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“…A comparison of 5-ASA pharmacokinetics in healthy adults; adults with CD and adults with UC showed that the time to reach the colon was faster with greater overall exposure for the diseased patients compared to the healthy controls [55]. This increased exposure is likely to be due to a combination of factors: an increase in permeability due to the inflamed mucosa or the reduction in viscosity of the colonic fluids in patients with CD or UC or the greater frequency of propagating contractions in the colon [56,57].…”

Section: Strengths and Limitations Of The Modelmentioning

confidence: 99%

Modelling and Simulation of the Drug Release from a Solid Dosage Form in the Human Ascending Colon: The Influence of Different Motility Patterns and Fluid Viscosities

et al. 2021

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For colonic drug delivery, the ascending part of the colon is the most favourable site as it offers the most suitable environmental conditions for drug dissolution. Commonly, the performance of a drug formulation is assessed using standardised dissolution apparatus, which does not replicate the hydrodynamics and shear stress evoked by wall motion in the colon. In this work, computer simulations are used to analyse and understand the influence of different biorelevant motility patterns on the disintegration/drug release of a solid dosage form (tablet) under different fluid conditions (viscosities) to mimic the ascending colonic environment. Furthermore, the ability of the motility pattern to distribute the drug in the ascending colon luminal environment is analysed to provide data for a spatiotemporal concentration profile. The motility patterns used are derived from in vivo data representing different motility patterns in the human ascending colon. The applied motility patterns show considerable differences in the drug release rate from the tablet, as well as in the ability to distribute the drug along the colon. The drug dissolution/disintegration process from a solid dosage form is primarily influenced by the hydrodynamic and shear stress it experiences, i.e., a combination of motility pattern and fluid viscosity. Reduced fluid motion leads to a more pronounced influence of diffusion in the tablet dissolution process. The motility pattern that provoked frequent single shear stress peaks seemed to be more effective in achieving a higher drug release rate. The ability to simulate drug release profiles under biorelevant colonic environmental conditions provides valuable feedback to better understand the drug formulation and how this can be optimised to ensure that the drug is present in the desired concentration within the ascending colon.

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Section: Strengths and Limitations Of The Modelmentioning

confidence: 99%

Modelling and Simulation of the Drug Release from a Solid Dosage Form in the Human Ascending Colon: The Influence of Different Motility Patterns and Fluid Viscosities

et al. 2021

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“…Moreover, GI disease can affect colonic physiology and function, and in turn affect drug behaviour and performance in patients [40][41][42][43][44]. For example, colonic pH is known to be reduced in IBD patients; changes to the epithelium and its transporters occur in colorectal cancer; and numerous diseases alter colonic transit time [9,45,46].…”

Section: The Colonic Environmentmentioning

confidence: 99%

“…In addition, patients with IBD display up to 20% longer small intestinal transit times [48], differing fluid volumes with constipation and/or diarrhoea, a higher colonic epithelial permeability [49], colonic inflammation [50] and reduced surface mucus [51]. An increasing body of research has reported that systemic diseases indirectly related to the GI tract such as cystic fibrosis, Parkinson's disease, diabetes mellitus, human immunodeficiency virus (HIV) and chronic pain can also influence gut function [40][41][42][43][44].…”

Section: The Colonic Environmentmentioning

confidence: 99%

Clinical translation of advanced colonic drug delivery technologies

Awad

Madla

McCoubrey

et al. 2022

Advanced Drug Delivery Reviews

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“…Furthermore, corticosteroids are an option for patients who fail to achieve remission with 5-ASA. Anti-tumor necrosis factor alpha (TNF-α) drugs such as infliximab are considered for patients who do not respond to corticosteroid therapy (Effinger et al, 2020). Despite considerable advances in the recognition and treatment of UC, the use of 5-ASA drugs such as mesalazine is still accompanied by a series of adverse events including inflammatory reactions, pancreatitis, cardiotoxicity, hepatotoxicity, musculoskeletal complaints, respiratory symptoms, nephropathies and sexual dysfunction (Sehgal, et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Ilex rotunda Thunb Protects Against Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice by Restoring the Intestinal Mucosal Barrier and Modulating the Oncostatin M/Oncostatin M Receptor Pathway

Yang

Yuan³

et al. 2022

Front. Pharmacol.

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Ilex rotunda Thunb (IR) is a traditional Chinese medicine used for the clinical treatment of gastric ulcers and duodenal ulcers; however, the effect of IR on ulcerative colitis (UC) and its underlying mechanism remains unclear. This study investigated the therapeutic effect of IR on UC mice induced by dextran sulfate sodium (DSS) as well as the potential underlying mechanism. The main components of IR were analyzed by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Then we established a model of UC mice by administering 2.0% DSS for 7 days followed by 2 weeks of tap water for three cycles and administered IR. On day 56, the disease activity index (DAI), colon length, pathological changes, and inflammatory response of the colon tissue of mice were assessed. The oxidative stress and apoptosis of colon tissue were detected, and the integrity of the intestinal mucosal barrier was evaluated to assess the effect of IR. Furthermore, the relationship between oncostatin M (OSM) and its receptor (OSMR) in addition to the IR treatment of UC were evaluated using a mouse model and Caco2 cell model. The results showed that IR significantly alleviated the symptoms of UC including rescuing the shortened colon length; reducing DAI scores, serum myeloperoxidase and lipopolysaccharide levels, pathological damage, inflammatory cell infiltration and mRNA levels of interleukin one beta, tumor necrosis factor alpha, and interleukin six in colon tissue; alleviating oxidative stress and apoptosis by decreasing kelch-like ECH-associated protein 1 expression and increasing nuclear factor-erythroid factor 2-related factor 2 and heme oxygenase-1 protein expression; and promoting the regeneration of epithelial cells. IR also promoted the restoration of the intestinal mucosal barrier and modulated the OSM/OSMR pathway to alleviate UC. It was found that IR exerted therapeutic effects on UC by restoring the intestinal mucosal barrier and regulating the OSM/OSMR pathway.

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Gastrointestinal diseases and their impact on drug solubility: Ulcerative Colitis

Cited by 6 publications

References 57 publications

Modelling and Simulation of the Drug Release from a Solid Dosage Form in the Human Ascending Colon: The Influence of Different Motility Patterns and Fluid Viscosities

Modelling and Simulation of the Drug Release from a Solid Dosage Form in the Human Ascending Colon: The Influence of Different Motility Patterns and Fluid Viscosities

Clinical translation of advanced colonic drug delivery technologies

Ilex rotunda Thunb Protects Against Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice by Restoring the Intestinal Mucosal Barrier and Modulating the Oncostatin M/Oncostatin M Receptor Pathway

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