Meta-analysis of Magnetic Marker Monitoring Data to Characterize the Movement of Single Unit Dosage Forms Though the Gastrointestinal Tract Under Fed and Fasting Conditions

Hénin, Émilie; Bergstrand, Martin; Karlsson, Mats O.

doi:10.1007/s11095-015-1824-x

Cited by 13 publications

(10 citation statements)

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“…new formulations) while accounting for the effect of covariates and the between subject variability in GI transit and pH. To perform these simulations the in silico model was used along with a previously developed continuous Markov model describing the GI transit of solid dosage form under fasting and postprandial status (8). This implementation enables the simulation of new clinical trial design, which could be used to explore the HPMC release under different food patterns or with multiple tablet administration.…”

Section: Discussionmentioning

confidence: 99%

“…In order to generate a high number of new MMM GI location profiles, a first set of simulations were run from a previously published Markov model describing the GI transit of solid dosage form in fasting and postprandial status (8). The HPMC release profiles were then simulated by using the newly generated GI location profiles in the in vivo tablet erosion model.…”

Section: Methodsmentioning

confidence: 99%

“…MMM relies on the measurement of the magnetic dipole generated by a magnetically labeled dosage form (7–9). More recently the MMM technique has been used to predict the in vivo GI transit of solid dosage form under different prandial statuses using in silico models (8). …”

Section: Introductionmentioning

confidence: 99%

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In Vitro and In Vivo Modeling of Hydroxypropyl Methylcellulose (HPMC) Matrix Tablet Erosion Under Fasting and Postprandial Status

et al. 2017

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PurposeTo develop a model linking in vitro and in vivo erosion of extended release tablets under fasting and postprandial status.MethodsA nonlinear mixed-effects model was developed from the in vitro erosion profiles of four hydroxypropyl methylcellulose (HPMC) matrix tablets studied under a range of experimental conditions. The model was used to predict in vivo erosion of the HPMC matrix tablets in different locations of the gastrointestinal tract, determined by magnetic marker monitoring. In each gastrointestinal segment the pH was set to physiological values and mechanical stress was estimated in USP2 apparatus rotation speed equivalent.ResultsErosion was best described by a Michaelis–Menten type model. The maximal HPMC release rate (VMAX) was affected by pH, mechanical stress, HPMC and calcium hydrogen phosphate content. The amount of HPMC left at which the release rate is half of VMAX depended on pH and calcium hydrogen phosphate. Mechanical stress was estimated for stomach (39.5 rpm), proximal (93.3 rpm) and distal (31.1 rpm) small intestine and colon (9.99 rpm).ConclusionsThe in silico model accurately predicted the erosion profiles of HPMC matrix tablets under fasting and postprandial status and can be used to facilitate future development of extended release tablets.Electronic supplementary materialThe online version of this article (doi:10.1007/s11095-017-2113-7) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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In Vitro and In Vivo Modeling of Hydroxypropyl Methylcellulose (HPMC) Matrix Tablet Erosion Under Fasting and Postprandial Status

et al. 2017

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“…Besides intraluminal drug concentration profiling of the drug, magnetic resonance imaging (MRI) was used as a robust tool to assess (i) the volume of GI fluids present in the human GI tract and (ii) the gastric emptying and intestinal transit times of specific dosage forms (when magnetically labeled) (21,22). The measured volumes along the GI tract are extremely valuable as these fluids are necessary for a drug to dissolve; a drug needs to dissolve in the intestinal fluids before being eligible for intestinal permeation (23).…”

Section: Wp 3-in Vivo Toolsmentioning

confidence: 99%

Leveraging Oral Drug Development to a Next Level: Impact of the IMI-Funded OrBiTo Project on Patient Healthcare

et al. 2021

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A thorough understanding of the behavior of drug formulations in the human gastrointestinal (GI) tract is essential when working in the field of oral drug development in a pharmaceutical company. For orally administered drug products, various GI processes, including disintegration of the drug formulation, drugrelease, dissolution, precipitation, degradation, dosage form transit and permeation, dictate absorption into the systemic circulation. These processes are not always fully captured in predictive in vitro and in silico tools, as commonly applied in the pre-clinical stage of formulation drug development. A collaborative initiative focused on the science of oral biopharmaceutics was established in 2012 between academic institutions and industrial companies to innovate, optimize and validate these in vitro and in silico biopharmaceutical tools. From that perspective, the predictive power of these models can be revised and, if necessary, optimized to improve the accuracy toward predictions of the in vivo performance of orally administered drug products in patients. The IMI/EFPIA-funded “Oral Bioavailability Tools (OrBiTo)” project aimed to improve our fundamental understanding of the GI absorption process. The gathered information was integrated into the development of new (or already existing) laboratory tests and computer-based methods in order to deliver more accurate predictions of drug product behavior in a real-life setting. These methods were validated with the use of industrial data. Crucially, the ultimate goal of the project was to set up a scientific framework (i.e., decision trees) to guide the use of these new tools in drug development. The project aimed to facilitate and accelerate the formulation development process and to significantly reduce the need for animal experiments in this area as well as for human clinical studies in the future. With respect to the positive outcome for patients, high-quality oral medicines will be developed where the required dose is well-calculated and consistently provides an optimal clinical effect. In a first step, this manuscript summarizes the setup of the project and how data were collected across the different work packages. In a second step, case studies of how this project contributed to improved knowledge of oral drug delivery which can be used to develop improved products for patients will be illustrated.

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“…[4][5][6] More recently, magnetic marker monitoring methods have been introduced and the GI transit characteristics of magnetically labeled solid dosage forms have been reported in the literature. 7,8 Furthermore, telemetric capsules such as SmaprtPill® (Medtronic, Minneapolis, MN) and IntelliCap® (Medimetrics, Eindhoven, Netherlands), which can record pH, temperature, and so forth, have been used to characterize the GI transit of these capsules in humans. 9,10 The effect of food on the oral pharmacokinetics (PK) of a large number of drugs has been widely recognized.…”

Section: Introductionmentioning

confidence: 99%

Effects of Diurnal Variation and Food on Gastrointestinal Transit of 111In-Labeled Hydrogel Matrix Extended-Release Tablets and 99mTc-Labeled Pellets in Humans

Kambayashi

Sako²,

Kondo

2020

Journal of Pharmaceutical Sciences

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Meta-analysis of Magnetic Marker Monitoring Data to Characterize the Movement of Single Unit Dosage Forms Though the Gastrointestinal Tract Under Fed and Fasting Conditions

Abstract: This model-based knowledge can be used as a part of mechanism-based models for drug absorption, applied for bottom-up predictions and/or top-down estimation.

Cited by 13 publications

References 47 publications

In Vitro and In Vivo Modeling of Hydroxypropyl Methylcellulose (HPMC) Matrix Tablet Erosion Under Fasting and Postprandial Status

In Vitro and In Vivo Modeling of Hydroxypropyl Methylcellulose (HPMC) Matrix Tablet Erosion Under Fasting and Postprandial Status

Leveraging Oral Drug Development to a Next Level: Impact of the IMI-Funded OrBiTo Project on Patient Healthcare

Effects of Diurnal Variation and Food on Gastrointestinal Transit of 111In-Labeled Hydrogel Matrix Extended-Release Tablets and 99mTc-Labeled Pellets in Humans

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