Abstract:The performance of solid oral dosage forms targeting the colon is typically evaluated using standardised pharmacopeial dissolution apparatuses. However, these fail to replicate colonic hydrodynamics. This study develops a digital twin of the Dynamic Colon Model; a physiologically representative in vitro model of the human proximal colon. Magnetic resonance imaging of the Dynamic Colon Model verified that the digital twin robustly replicated flow patterns under different physiological conditions (media viscosit… Show more
“…However, the stimulated colon may generate hydrodynamic conditions that lie somewhere between 25 and 50 rpm. This data builds upon previous conclusions that the use of > 50 rpm in the USPII is not recommended for colon-targeted dosage forms [ 10 ].…”
Section: Resultssupporting
confidence: 84%
“…Higher release was achieved in the USPII at 25, 50 and 100 rpm. Although conclusions cannot be drawn on the shear rates likely to have occurred from this comparison, since a constant shear is applied in the USPII and shear in the DCM has a high spatiotemporal dependence [ 10 ]. Previous MRI studies of the DCM found velocities to vary from −2.16–0.78 cm s −1 and shear rate fluctuating between 0–8 s −1 when slower CPPWs were applied (0.4 and 0.8 cm s −1 ) at the same volume and viscosity as in this study.…”
Section: Resultsmentioning
confidence: 99%
“…In addition, a low amplitude cyclic antegrade propagating wave (CPPW) travelling the 28 cm length of the DCM (mimicking from caecum to hepatic flexure) has been used in previous studies [ 10 , 11 , 12 ]. Its motility was based on observations from a high resolution manometry study on healthy volunteers by Dinning et al [ 13 ].…”
The in vitro release of theophylline from an extended-release dosage form was studied under different hydrodynamic conditions in a United States Pharmacopoeial (USP) dissolution system II and a bespoke in vitro tubular model of the human colon, the Dynamic Colon Model (DCM). Five biorelevant motility patterns extracted from in vivo data were applied to the DCM, mimicking the human proximal colon under baseline conditions and following stimulation using polyethylene glycol or maltose; these represent the lower and upper bounds of motility normally expected in vivo. In the USPII, tablet dissolution was affected by changing hydrodynamic conditions at different agitation speeds of 25, 50 and 100 rpm. Applying different motility patterns in the DCM affected the dissolution profiles produced, with theophylline release at 24 h ranging from 56.74 ± 2.00% (baseline) to 96.74 ± 9.63% (maltose-stimulated). The concentration profiles of theophylline were markedly localized when measured at different segments of the DCM tube, highlighting the importance of a segmented lumen in intestine models and in generating spatial information to support simple temporal dissolution profiles. The results suggested that the shear stresses invoked by the unstimulated, healthy adult human colon may be lower than those in the USPII at 25 rpm and thus insufficient to achieve total release of a therapeutic compound from a hydroxyethyl cellulose matrix. When operated under stimulated conditions, drug release in the DCM was between that achieved at 25 and 50 rpm in the USPII.
“…However, the stimulated colon may generate hydrodynamic conditions that lie somewhere between 25 and 50 rpm. This data builds upon previous conclusions that the use of > 50 rpm in the USPII is not recommended for colon-targeted dosage forms [ 10 ].…”
Section: Resultssupporting
confidence: 84%
“…Higher release was achieved in the USPII at 25, 50 and 100 rpm. Although conclusions cannot be drawn on the shear rates likely to have occurred from this comparison, since a constant shear is applied in the USPII and shear in the DCM has a high spatiotemporal dependence [ 10 ]. Previous MRI studies of the DCM found velocities to vary from −2.16–0.78 cm s −1 and shear rate fluctuating between 0–8 s −1 when slower CPPWs were applied (0.4 and 0.8 cm s −1 ) at the same volume and viscosity as in this study.…”
Section: Resultsmentioning
confidence: 99%
“…In addition, a low amplitude cyclic antegrade propagating wave (CPPW) travelling the 28 cm length of the DCM (mimicking from caecum to hepatic flexure) has been used in previous studies [ 10 , 11 , 12 ]. Its motility was based on observations from a high resolution manometry study on healthy volunteers by Dinning et al [ 13 ].…”
The in vitro release of theophylline from an extended-release dosage form was studied under different hydrodynamic conditions in a United States Pharmacopoeial (USP) dissolution system II and a bespoke in vitro tubular model of the human colon, the Dynamic Colon Model (DCM). Five biorelevant motility patterns extracted from in vivo data were applied to the DCM, mimicking the human proximal colon under baseline conditions and following stimulation using polyethylene glycol or maltose; these represent the lower and upper bounds of motility normally expected in vivo. In the USPII, tablet dissolution was affected by changing hydrodynamic conditions at different agitation speeds of 25, 50 and 100 rpm. Applying different motility patterns in the DCM affected the dissolution profiles produced, with theophylline release at 24 h ranging from 56.74 ± 2.00% (baseline) to 96.74 ± 9.63% (maltose-stimulated). The concentration profiles of theophylline were markedly localized when measured at different segments of the DCM tube, highlighting the importance of a segmented lumen in intestine models and in generating spatial information to support simple temporal dissolution profiles. The results suggested that the shear stresses invoked by the unstimulated, healthy adult human colon may be lower than those in the USPII at 25 rpm and thus insufficient to achieve total release of a therapeutic compound from a hydroxyethyl cellulose matrix. When operated under stimulated conditions, drug release in the DCM was between that achieved at 25 and 50 rpm in the USPII.
“… 22 The Blue Brain Project, for example, began in 2005 as a collaboration between EPFL (Ecole Polytechnique Fédérale de Lausanne) and International Business Machines and aims to model the neocortical column. 23 Schütt et al 24 developed a DT of the Dynamic Colon Model that considered media viscosity, and peristaltic wave speed. It provided new insights for dissolution testing beyond established pharmacopoeial methods.…”
As simulation is playing an increasingly important role in medicine, providing the individual patient with a customised diagnosis and treatment is envisaged as part of future precision medicine. Such customisation will become possible through the emergence of digital twin (DT) technology. The objective of this article is to review the progress of prominent research on DT technology in medicine and discuss the potential applications and future opportunities as well as several challenges remaining in digital healthcare. A review of the literature was conducted using PubMed, Web of Science, Google Scholar, Scopus and related bibliographic resources, in which the following terms and their derivatives were considered during the search: DT, medicine and digital health virtual healthcare. Finally, analyses of the literature yielded 465 pertinent articles, of which we selected 22 for detailed review. We summarised the application examples of DT in medicine and analysed the applications in many fields of medicine. It revealed encouraging results that DT is being increasing applied in medicine. Results from this literature review indicated that DT healthcare, as a key fusion approach of future medicine, will bring the advantages of precision diagnose and personalised treatment into reality.
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