A Formulation Case Study Comparing the Dynamic Gastric Model with Conventional Dissolution Methods

Mann, James; Pygall, Samuel R.

doi:10.14227/dt190412p14

Cited by 25 publications

(9 citation statements)

References 16 publications

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“…A good overview on those systems addressing hydrodynamic conditions of the GI has been provided by Pentafragka et al (3). Some outstanding models that allow dissolution profiling of oral solid dosage forms under dynamic conditions are the fed stomach model (FSM) by Koziolek et al, the dynamic gastric model (DGM) from the Institute for Food Research (Norwich, UK), and the TIM-1 model from TNO Triskelion (7)(8)(9)(10)(11).…”

Section: Determination Of Dissolution Profile and Bioaccessibility Ofmentioning

confidence: 99%

Determination of Dissolution Profile and Bioaccessibility of Ketosteril Using an Advanced Gastrointestinal In Vitro Model

Fuente¹,

Secouard²,

Siegert³

et al. 2019

Dissolution Technol.

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Ketosteril is an originator drug prescribed for nutrition therapy for patients with chronic kidney disease (CKD). Ketoanalogues (KAs) of amino acids are part of the active pharmaceutical ingredients in the Ketosteril film-coated tablets. The in vitro dissolution and gastrointestinal (GI) release of KAs available in Ketosteril were determined in this study using a dynamic multi-compartmental system, TIM-1. A water-fed mode of operation for TIM-1 was used to study the dissolution and bioaccessibility of KA during an experimental 5-hour test. Overall recovery (i.e., mass balance) and bioaccessibility as a function of time were the major outcome parameters. Based on eight experimental runs, the mean ± SD percent recovery was 95.2 ± 4.0 (RSD: 4.2), showing high reproducibility for the dissolution of a solid dosage form in a highly complex in vitro model. The bioaccessible fraction (BioAcc) of KA was found to be highest at 2 and 3 hours. Furthermore, the total BioAcc was found to be higher for the jejunum (68.2%-68.7% of dosage) than the ileum (15.9%-17.9% of dosage). The in vitro results of this study show that the release of Ketosteril KAs occurs at physiological relevant sites, mainly the jejunum, with its amino acid receptor for absorption, as it has been reported in clinical observations with humans. These bioaccessibility results may explain the clinical performance of Ketosteril reported in several clinical trials of patients with CKD with regards to postponing dialysis. Ketosteril in combination with a low protein diet has been proved to be a nutritionally safe therapy.

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Section: Determination Of Dissolution Profile and Bioaccessibility Ofmentioning

confidence: 99%

Determination of Dissolution Profile and Bioaccessibility of Ketosteril Using an Advanced Gastrointestinal In Vitro Model

Fuente¹,

Secouard²,

Siegert³

et al. 2019

Dissolution Technol.

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“…Current in vitro methods used in the study of disintegration and dissolution of oral solid dosage forms do not provide a physiological representation of the dynamic biochemical and physical environment of the human stomach (Vardakou et al 2011a ) and are therefore sometimes not predictive of the in vivo behaviour of dosage forms, particularly in the case of dosing with or after a typical meal. The DGM is well placed to bridge the gap between these simpler dissolution tests and in vivo studies (animal or human) and can be used in either to explain unexpected in vivo results, or as a predictive tool (Mann and Pygall 2012 ;Wickham et al 2009 ).…”

Section: Pharmaceutical-based Researchmentioning

confidence: 99%

Dynamic Gastric Model (DGM)

Thuenemann

Mandalari

Rich

et al. 2015

The Impact of Food Bioactives on Health

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The Dynamic Gastric Model (DGM) was developed at the Institute of Food Research (Norwich, UK) to address the need for an in vitro model which could simulate both the biochemical and mechanical aspects of gastric digestion in a realistic time-dependent manner. As in the human stomach, masticated material is processed in functionally distinct zones: Within the fundus/main body of the DGM, gastric acid and enzyme secretions are introduced around the outside of the food bolus which is subjected to gentle, rhythmic massaging. Secretion rates adapt dynamically to the changing conditions within this compartment (acidifi cation, fi ll state). Portions of gastric contents are then moved into the DGM antrum where they are subjected to physiological shear and grinding forces before ejection from the machine (and subsequent separate duodenal processing).The DGM has been used extensively for both food and pharmaceutical applications, to study, for example, release and bioaccessiblity of nutrients and drugs. The system allows the use of complex food matrices (as used in in vivo studies) and processes these under physiological conditions in real-time, thereby providing a realistic tool for the simulation of human gastric digestion.

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“…In this study (17), the intention was to create a bilayer tablet containing multiple APIs in an immediate-release (IR) layer and a nondisintegrating controlled-release layer, then match the in vivo performance of a reference product of the drug contained within the immediate-release layer. In USP dissolution Apparatus 2 ( Figure 3A), the immediate-release layer behaved similarly when compressed as a single-entity tablet or a bilayer formulation.…”

Section: Bioequivalence Of Complex Dosage Formsmentioning

confidence: 99%

The Design, Operation, and Application of a Dynamic Gastric Model

Wickham¹,

Faulks²,

Mann³

et al. 2012

Dissolution Technol.

112

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The mechanical functioning of the stomach has been well researched (1). The contractions that mix, break up, and propel the gastric bolus in the main body and antrum have been described in detail and have been partially modeled mathematically. Because the antral forces are particularly important in the mixing and break up of food, they have been measured using manometers, pressure transducers, MRI imaging of agar beads of differing strength (2), and other methods (3, 4). The chemical and biochemical environment of the stomach, its acid and digestive enzymes, and their production and activity rates under different conditions have been studied for many years, and reference ranges established mainly for diagnostic purposes. All these areas have been extensively reviewed (5-7).Despite this understanding of gastric function, many in vitro digestion studies use grossly simplified systems that often include food homogenization, nonphysiological mixing and shear, and unrealistic acid and enzyme concentrations that do not change over time as happens in vivo.This paper describes the design and operation of a computer-controlled dynamic gastric model (DGM) that was built to investigate the effects of the biochemical and physical processing of foods and oral pharmaceuticals.Our intention was to draw together the physical and biochemical features of the human stomach with data on gastric residence time and emptying profiles and to design a computer-controlled mechanical stimulation that works in real time with realistic chewed foods or meals and oral pharmaceutical and nutraceutical products.

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A Formulation Case Study Comparing the Dynamic Gastric Model with Conventional Dissolution Methods

Cited by 25 publications

References 16 publications

Determination of Dissolution Profile and Bioaccessibility of Ketosteril Using an Advanced Gastrointestinal In Vitro Model

Determination of Dissolution Profile and Bioaccessibility of Ketosteril Using an Advanced Gastrointestinal In Vitro Model

Dynamic Gastric Model (DGM)

The Design, Operation, and Application of a Dynamic Gastric Model

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