Abstract
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.
Highlights
The number of people worldwide affected by colonic diseases such as inflammatory bowel disease (IBD) (i.e., Crohn’s disease (CD) and ulcerative colitis (UC)) has steadily increased from 3.7 million in 1990 to 6.8 million in 2017 [1]
This study describes the development of a computational model to describe the drug release from and the disintegration of a solid dosage form and the distribution of the Active Pharmaceutical Ingredient (API) in the environment of the ascending colon
This applies to the different motility patterns that occur in the colonic environment [9]
Summary
The number of people worldwide affected by colonic diseases such as inflammatory bowel disease (IBD) (i.e., Crohn’s disease (CD) and ulcerative colitis (UC)) has steadily increased from 3.7 million in 1990 to 6.8 million in 2017 [1]. Colon-specific drug delivery has been the focus of numerous studies in recent years (e.g., [2,3]), as it offers opportunities to improve the treatment of local diseases such as CD and UC while minimizing side effects at the same time [4]. The oral route, due to its convenience, is the primary method of administration for most medicines, including those that target the colon. The proximal colon is the Pharmaceutics 2021, 13, 859.
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