Artificial Stomach Research Articles

Relative Bioavailability Assessment of Solid Forms by An Artificial Stomach and Duodenum Apparatus

In this work, the ability of the artificial stomach and duodenum (ASD) model to predict bioavailability in rats was investigated using a poorly soluble model compound, BI-639667. A solution and four suspensions of different solid forms of BI-639667 were tested both in an ASD and rats. Rank order of the bioavailability estimated from an ASD apparatus is consistent with that of in vivo result in rats, i.e., solution > salicylic acid cocrystal > malate salt > maleate salt > monohydrate, which correlates with the ability of the different solid forms to maintain supersaturation with respect to the stable form in aqueous solution. The results support the use of an ASD for characterizing dissolution performance of solid forms to aid their selection for tablet formulation development.

Development details of an Artificial Gastric Digestive System (AGDS) and analysis of model food disintegration and degradation

SummaryThe individual differences and ethical limitations of in vivo studies have prompted the development of in vitro digestive models. In this study, an Artificial Gastric Digestive System (AGDS) with the geometry and motion of the human stomach was designed and operated. Five agar beads with different breaking forces (0.35–0.95 N) were applied in AGDS model to verify the gastric breakdown behaviour. Results showed that the degradation degree of agar beads in AGDS was significantly different to that in the shaking water bath. Besides, beads in a high‐viscosity medium (30 Pa·s) had a shorter breaking time (26 min) than that in a low‐viscosity medium (0.69 Pa·s, 37 min). AGDS can simulate peristalsis and dynamic flow kinetics, thus it pushes forward the understanding of food degradation and nutrients release during gastric digestion and may inspire the design of versatile artificial stomach based on specific populations.

IN SILICO AND IN VIVO VALIDATION OF DIGESTION BEHAVIOR OF RICE IN THE ARTIFICIAL STOMACH ARK®

The effect of the physicochemical properties on the digestion behavior of rice was evaluated using the artificial stomach response kit (ARK®). Due to the presence of the external bran layer, brown rice (Rv3) showed delayed rates of gastric emptying, apart from a higher half emptying time (101.80 ± 1.20 min) than milled rice (Rv1 - 57.84 ± 7.49 min) and basmati rice (Rv2 - 77.93 ± 10.18 min). The bran layer of Rv3 inhibited the diffusion of the simulated gastric fluid and resulted in lesser particle breakdown and low glycemic index (GI). In comparison with the shaker digestion process, the mechanical force produced in the ARK® resulted in a higher degree of particle breakdown. An in silico approach successfully predicted the glucose response pattern of rice varieties with no statistical difference (at p< 0.05) with the human in vivo datasets using the output obtained from ARK®. The GI obtained from ARK® was validated with in vivo data using Bland Altmann’s statistical tool which showed good agreement. The morphology, dimensions, capacity of the stomach chamber in the ARK® also resembled in vivo observations. The ARK® is proposed as an improved alternative for in vitro digestion studies.

Aerated whey protein gels as a controlled release system of creatine investigated in an artificial stomach

A controlled creatine-release system has been developed from whey protein-based gels. Their functionalization was carried out by aeration and sodium ions induced “cold gelation” processes. The effect of protein concentration in the aerated whey protein gels at pH 7.0 and 8.0 was analyzed. Physicochemical properties of the aerated gels were evaluated. It was possible to obtain the ions induced whey protein aerated gel with well distributed creatine and different microstructure as well as rheological properties. Different protein concentrations and pH enabled obtaining gels with different rheological properties, texture, air fraction, diameter of air bubbles, microstructure and surface roughness. An increase in the protein concentration enhanced the hardness of the samples, regardless of their pH. The mechanical strength of gels prepared at pH 8 were higher than those obtained at pH 7, as was manifested by the smaller storage modulus of the latter. The former gel exhibited a microstructure between particulate and fine-stranded. A stronger gel matrix produced smaller air bubbles. Aerated gels produced at pH 7.0 had higher roughness than those obtained at pH 8.0. Optimal conditions for inclusion of air bubbles into the gel matrix were: 9% protein concentration at pH 8.0 and this aerated gel was selected for digestion in the artificial stomach. There is a small conversion of creatine to creatinine in the artificial stomach digestion process (9.6% after 6 h). The diffusion of creatine crystals from the aerated gel matrix was the mechanism responsible for the release process. Aerated whey protein gels can be used as matrices for time extended releasing of creatine in the stomach.

Profound effects of gastric secretion rate variations on the precipitation of erlotinib in duodenum – An in vitro investigation

Using an artificial stomach and duodenum (ASD), we investigated the pH-dependent precipitation of erlotinib (ERL) during dissolution in the gastrointestinal (GI) tract by varying the rate of gastric fluid secretion (RGFS). Results show that decreasing RGFS from 2.5 to 0.5 mL/min leads to an increased degree of supersaturation in the duodenum fluid due to elevated pH, resulting in precipitation of ERL and a reduced area under the curve (AUC) of the concentration – time profiles from 14,000 to 3,000 (μg‧min)/mL. Such a change in AUC is expected to lower the bioavailability of ERL, a BCS II drug, in patients with a low RGFS. This example demonstrates the potential use of ASD as an effective tool for guiding the efficient development of robust tablet formulations by better understanding the impact of GI tract pH on the fate of drugs in the duodenal fluid.

Onset of the neutralising action of antacids based on calcium and magnesium carbonate using an artificial stomach model

The in-vitro study evaluated the onset of the neutralising action of the antacid Rennie® as compared to a placebo. Among other things, the results showed a rise in the pH of the artificial stomach liquid from pH 1 to over 3 within 40 seconds after application of the antacid. The maximum pH of 5.24 was maintained over a period of approximately 10 minutes. At the same time, lower activity levels of mucosa-damaging pepsin were measured [3].

Onset of the neutralising action of antacids based on calcium and magnesium carbonate using an artificial stomach model

Die In-vitro-Untersuchung bewertete das Einsetzen des neutralisierenden Effekts des Antazidums Rennie® im Vergleich zu Placebo. Die Ergebnisse verzeichneten unter anderem innerhalb von 40 Sekunden einen Anstieg des pH der künstlichen Magenflüssigkeit nach der Applikation des Antazidums von pH 1 auf über 3. Der maximale pH von 5,24 wurde über eine Zeit von etwa 10 Minuten aufrechterhalten. Zeitgleich wurde eine geringere Aktivität des Mucosa-schädigenden Pepsins gemessen [3].

Some improvements in the technique of creating an "artificial stomach" from the small intestine in partial and total resections of the stomach

The literature of recent decades about the long-term consequences of partial and total resections of the stomach clearly indicates that a significant part of patients after these operations have persistent digestive disorders. The developing peculiar complex symptom complex is designated by various names: "agastral asthenia" (A. A. Busalov, M. S. Govorova), "resection disease" (G. G. Karavanov and O. V. Filts), "hyperglycemic syndrome" (OL Gordon), "hypoglycemic syndrome"; in foreign literature, the term "dumping syndrome" or "postgastrectomy syndrome" is often used.

An investigation on gastric emptying behavior of apple in the dynamic digestion model ARK® and its validation using MRI of human subjects – A pilot study

The employment of dynamic digestion models for understanding the digestion behavior of foods has become an emerging trend in recent times, as the in vivo techniques used currently pose safety and ethical concerns. On the other hand, it is equally important to validate the mentioned digestion models, so that they can aid in assessing various aspects of digestion. Hence, this study was planned to investigate the gastric emptying behavior of apples in a 3D printed stomach in vitro dynamic digestion model artificial stomach response kit. Further, the obtained results are validated by studying the gastric emptying behavior of apples in healthy and adult human individuals. Gastric emptying trends in both the in vivo and in vitro trials showed close half emptying times, i.e., 51.00 ± 7.54 and 57.84 ± 4.41 min respectively. Also, Tlag, K, β obtained were similar in both the in vivo and in vitro experiments. In addition to that, a strong positive correlation is noticed between the in vivo and in vitro trials, r = 0.99. Upon successful validation with foods having diversified properties, the ARK® model can be complementary for in vivo techniques to understand the gastric emptying behavior and other digestion aspects of foods.

Tracking the digestive performance of different forms of dairy products using a dynamic artificial gastric digestive system

This study aimed to explore the digestive behaviour of different forms of dairy products using an independent-developed artificial gastric digestion system (AGDS). It was found that the pH of UHT milk, yogurt and cheese increased to 6.5, 4.2 and 5.7, respectively, at the beginning of gastric digestion, while the value of cheese showed slower decreased rate than the other dairy products with the time extension. Protein in liquid (milk) and semi-liquid (yogurt) dairy was obviously hydrolyzed in the simulated stomach, whereas, the proteins were coagulated and slow-degraded in solid product (cheese) under gastric conditions. The fat globule quickly released from the UHT milk and distributed relevant uniform alongside the protein particles, while it wrapped in protein network and no obviously coalescence was found in yogurt. The fat in the cheese was slower release and lots of free fat aggregated in the continuous phase at the end of digestion. Results indicated that the artificial stomach could provide useful information for the design of dairy and other food matrices linking the structure and controlled release of nutrients in the stomach.

Results of selection work with grain crops in the subarctic zone of the Russian Federation

Agriculture of the Northern regions specializes in animal husbandry, in this regard an urgent problem of crop production in the conditions of the Northern regions of the Russian Federation is the creation of precocious, high-yielding varieties of grain crops for fodder purposes. The article reflects the selection achievements in grain crops over the past seven years. The presented new varieties combine high yield, increased environmental plasticity, and have the ability to reduce their productivity to a lesser extent when cultivated in the harsh conditions of the Northern region. Breeding work conducted at the laboratory of crop production of the Primorskiy filial FGBUN FICKIA RAN - ArhNIISKH in 2005-2019, in breeding semipolar rotation in accordance with the "Guidelines on the selection of barley and oats" (2014), methodology of State Commission for testing of agricultural crops (1985). The digestibility of winter rye dry matter was determined by in vitro method on an artificial stomach. Statistical processing of experimental results was performed using the AGROS version 2.07 selection and genetic software package. Results of the study. As a result of selection work, precocious productive varieties of grain crops of the feed direction were bred and included in the state register. Bereginya — new-generation winter rye variety, universal use, with a low content of water-soluble pentosans in the grain. The variety has been included in the State register of selection achievements since 2013. Variety of spring barley Tausen — feed direction, resistant to environmental stress factors, high-yielding, resistant to lodging and pathogens (dusty smut, spotting). It has been included in the State register of selection achievements since 2014. Spring barley variety Kotlassky — feed direction precocious, productive, adaptive to adverse environmental factors, for obtaining concentrated feed for livestock and poultry. It has been included in the State register of breeding achievements since 2019. Arhan spring oat variety — environmentally plastic adapted to changes in soil and climate conditions, immune to dusty smut, combines a high yield of grain and green mass. Since 2020, it has been included in the State register of selection achievements.

Onset of acid-neutralizing action of a calcium/magnesium carbonate-based antacid using an artificial stomach model: an in vitro evaluation

BackgroundCalcium carbonate antacids are potent over-the-counter antacids, made more effective by adding magnesium carbonate (as in Rennie, Bayer). However, published studies on their onset of action are scarce. Therefore, we carried out an in vitro study comparing Rennie and placebo under simulated conditions of the human stomach (artificial stomach model) to reconfirm the onset of action of Rennie.MethodsThe validated Simulator of the Human Intestinal Microbial Ecosystem apparatus (SHIME, ProDigest, Belgium) was used, comprising five reactors simulating different parts of the human gastrointestinal tract. Both Rennie and placebo were dosed at two tablets per incubation over six independent, 2-h stomach incubations each. Primary objectives: to evaluate the time required to achieve pH 3.0, 3.5, 4.0 and 4.5, as well as the maximum pH reached. Secondary objective: to evaluate pepsin activity over the entire 2-h gastric incubation.ResultsAfter addition of Rennie, the gastric medium reached a pH of 3.0 within 40 s. The maximum pH of 5.24 was maintained for almost 10 min. In contrast, the maximum pH with placebo was 1.28 during the entire gastric simulation. Furthermore, Rennie strongly reduced the activity of mucosa-damaging pepsin during the period of increased pH. With placebo, the lower pH resulted in consistently high loads of digested peptides, reflecting the high cumulative and instantaneous pepsin activity.ConclusionsNew data is a critical component in informed decision making. Our data confirm the high efficacy and fast onset of acid-neutralizing action of Rennie, which begins to work within seconds.

Drug release in vivo and efficacy evaluation of a new colon targeted powder of total saponins of Pulsatilla

Based on the anti-ulcerative colitis (UC) effect of total saponins of Pulsatilla (PTS), a pH dependent colonic targeting particle design powder of PTS was prepared. The core-shell composite particle design powder of PTS was prepared with pH sensitive polymer material Eudragit S100 superfine powder as shell and the drug as core. The release of PTS composite particle design powder was increased in the artificial colon fluid and decreased in the artificial stomach and small intestine fluid.In this paper, the release performance of Pulsatilla saponin D in PTS and the ulcerative colitis model induced by TNBS in rats were used to evaluate the targeting of PTS composite particle design powder in colon.The results showed that the content of Pulsatilla saponin D in colon tissue was significantly higher than that of the original drug group after oral administration of PTS composite particle design powder. The solubility of Pulsatilla saponin D in colon tissue was also higher than that in the stomach and small intestine. The peak time and retention time in vivo were prolonged, and the maximum blood concentration was decreased (Cmax). The effect of colonic targeting powder of PTS (50 mg/kg)on anti-ulcerative colitis induced by TNBS in SD rats was better than the original drug (200 mg/kg). Therefore, it is a great significance to make the PTS into colon targeted preparation for improving bioavailability, efficacy and reducing gastrointestinal stimulation.

Polyethylene glycol electrolyte lavage solution increases tablet dissolution of acetaminophen in an in vitro model mimicking acute poisoning

IntroductionPolyethylene glycol electrolyte lavage solution (PEG-ELS) is similar to pharmaceutical solvent propylene glycol and used following acute poisonings for whole bowel irrigation (e.g., “body stuffing”). This raises concern of PEG-ELS increasing solubility following acute ingestions of non-sustained release xenobiotics in the stomach. We theorized PEG-ELS increases solubility of acetaminophen in an in vitro stomach model. Material and methodsAn in vitro artificial stomach with 500 mL simulated gastric fluid and either 500 mL of sodium chloride 0.9% (group A) or 500 mL of PEG-ELS (group B). Ten non-sustained release acetaminophen tablets added with concentrations 0, 15, 45 and 90 min in triplicate. Mean concentrations and mean area under the curve (AUC) (mg-min/L to 90 min). ResultsIn control group A (normal saline + simulated gastric fluid) mean acetaminophen concentrations 0, 3, 13 and 36 mg/L at 0, 15, 45 and 90 min, respectively. In group B (PEG-ELS + simulated gastric fluid) mean acetaminophen concentrations 0, 34, 109 and 136 mg/L at 0, 15, 45 and 90 min, respectively (p < 0.05). Mean AUC 0-90 1385 [95% C.I. 990.5–1779] mg-min/L in control group A compared to mean AUC 0-90 in group B (PEG-ELS) 7673 mg-min/L [95% C.I. 4832–10513] (p < 0.05). DiscussionGroup B (PEG-ELS) with significantly higher mean acetaminophen concentrations and greater mean AUC compared to control group A (normal saline). ConclusionWe demonstrated increased mean acetaminophen concentrations and increased mean AUC of following exposure of PEG-ELS in an artificial stomach model.

Advances in In Vivo Predictive Dissolution Testing of Solid Oral Formulations: How Closer to In Vivo Performance?

Dissolution has become an indispensable tool to predict the in vivo performance of dosage form, especially in recent times, because of the increasing complexity of new drugs discovered. Several attempts have been made to modify dissolution, so that it mimics the in vivo behavior to maximum possible accuracy and minimizes the probability of in vivo bioequivalence failures. In this context, several advancements have been reported including drug dissolution/absorption simulating system, bionic system, dissolution/permeation model, biphasic dissolution system, Caco-2 cell monolayer in combination with compendial dissolution apparatus, artificial stomach duodenum model, dynamic gastric model, Netherlands Organization for Applied Scientific Research gastrointestinal model, and many more. The present review highlights the recent advancements in dissolution methods with a focus on in vivo predictive dissolution methods, their advantages and disadvantages, and key factors governing the results obtained. The impact of maintaining sink conditions and use of biorelevant media is also discussed briefly.

Lactobacillus gasseri from human milk with probiotic potential and some technological properties

In the current study, Lactobacillus gasseri MA-4 strain from human breast milk was evaluated for its probiotic potential and some technological properties. The strain was also evaluated for its virulency. The antimicrobial activity was tested against a wide range of clinical-human and food pathogenic bacteria, Candida species and various fish pathogens. High tolerance was observed by MA-4 strain for some essential parameters such as low pH, bile salts, artificial stomach and small intestine fluids conditions. The autoaggregation and coaggregation abilities of the strain were recorded as 95% and 45–55% respectively. The nisin sensitivity against nine different nisin concentrations (1.25–150 -μg/mL) was only observed at 100 and 150μg/mL. The strain exhibited high resistance to sodium benzoate (0.1% w/v), a commonly used food preservative. The supernatant of the strain showed high cholesterol assimilation ability with 75.66% at the 1% bile concentration. DPPH free radical reducing and the iron ion chelating activity of MA-4 strain were determined as 39.20% and 15.60% respectively. Amylase and β-1,3–1,4-glucanase (lichenase) enzymes activities were also obtained qualitatively. Consequently, MA-4 strain may be considered as a good candidate for probiotic cultures, biotherapeutic and bio-protective agents.

Исследование иммобилизации пробиотиков как метода их защиты и доставки в желудочно-кишечный тракт человека

The relevance of research is the experimental and analytical justification of the effectiveness of the joint use of biopolymers of animal and plant origin as a substrate in the process of immobilization of the association of probiotic cultures. Researches are executed in specialized laboratories of universities: Omsk GAU, Saratov GAU, SKFU. In the form of a substrate were used: gelatin, χ-carrageenan, low-esterified pectin, modified starch; as bioobjects are selected: L. acidophilus, B. Lactis, S. thermophilus. To obtain reliable and complete characteristics, a set of research methods was used in the work: physicochemical, sensory, and microbiological. Investigation of immobilization allowed to determine the optimal ratio of biopolymers as a carrier (substrate): pectin and gelatin, as 2:1; the total concentration of solids of the carrier solution (20.0 ± 0.5)% by weight. The total number of viable cells of probiotic microorganisms in membranes (plates) is an average of lg (11.0 ± 0.55). In order to extend the shelf life, the membranes were dried in a freeze dryer, with parameters: the temperature of the frozen product (–25 °C) and the residual pressure in the sublimate 0.013–0.133 kPa. Immobilization by microencapsulation of the association of probiotic cultures of L. acidophilus, B. Lactis and S. thermophilus into a gel of biopolymers: gelatin food, pectin gene LM 106 AS-YA, starch in a ratio of 5:1:1 was studied by microencapsulation. The obtained microcapsules were studied in imitated gastric and intestinal conditions, while the number of viable probiotic cells was determined at different times of their degradation. It was established that 20–25% of viable cells of probiotics were released from capsules in the "artificial stomach" phase, 75–80% in the "artificial bowel" phase. Innovative biotechnologies of milk based products for specialized nutrition are presented.

Mechanism for the Reduced Dissolution of Ritonavir Tablets by Sodium Lauryl Sulfate

Sodium lauryl sulfate (SLS) is an anionic surfactant widely used in pharmaceutical research as a dissolution enhancer for poorly soluble drugs. When SLS was used in ritonavir (RTV) tablet formulation to improve wetting, dissolution of RTV was surprisingly deteriorated in acidic media. To understand this unexpected phenomenon, a systematic investigation, including solubility determination, intrinsic dissolution rate measurement, dissolution in an artificial stomach and duodenum apparatus, and solid-state characterization, revealed the formation of a poorly soluble salt, [RTV2+][LS−]2, in an acidic environment. Solubilization of the poorly soluble RTV salt was observed when the concentration of SLS exceeded the critical micelle concentration. Thus, precipitation of [RTV2+][LS−]2 at a low pH and in presence of a low SLS concentration can lead to deteriorated bioavailability. This unintended negative effect on dissolution should be carefully considered when using SLS in a tablet formulation of a basic drug that can be ionized in gastric fluid.

Probiotic Properties of Lactobacillus Plantarum LRCC5193, a Plant-Origin Lactic Acid Bacterium Isolated from Kimchi and Its Use in Chocolates.

This study involves an investigation of the probiotic properties of lactic acid bacteria isolated from Kimchi, and their potential applications in chocolate. Lactobacillus plantarum-LRCC5193 (LP-LRCC5193) demonstrated a significantly higher degree of heat, acid, and bile acid tolerance compared to other Kimchi isolates. The intestinal adhesion assay also revealed that 84.2 log percentage of LP-LRCC5193 adhered to the Caco-2 cells after 2 h of incubation. Furthermore, the lyophilized LP-LRCC5193 maintained 92.9 log percentage and 97.2 log percentage survival rate within artificial stomach juice (pH 2.5, pepsin 0.04%) and artificial intestinal juice (oxgall 0.5%, trypsin 0.04%, and pancreatin 0.04%), respectively. Meanwhile, we also found that lyophilized LP-LRCC5193 incorporated in chocolate exhibited significantly higher survivability than lyophilized LP-LRCC5193 in both artificial gastric and intestinal juice under 1 to 3 hr incubation, where the survivability was within the range of 96.3 to 98.5 log percentage, and 98.8 to 98.9 log percentage, respectively. A 6-month storage test further revealed that LP-LRCC5193 demonstrated higher stability than the lyophilized LP-LRCC5103 in 3 different temperature ranges, where the final survival rates were 97.2 log percentage (20 °C), 89.2 log percentage (33 °C), and 94.4 log percentage (15 to 30 °C/wk). Altogether, our data suggest that chocolate can be used as a tasty delivery vehicle for delivering putative probiotic strain, LP-LRCC5193 to the gastrointestinal tract. PRACTICAL APPLICATION: Lactobacillus plantarum LRCC5193 (LP-LRCC5193) isolated from Kimchi demonstrated high stability under gastrointestinal environmental stresses and good adhesion to the intestinal epithelial cells in vitro. In addition, LP-LRCC5193 containing chocolates remained highly stable after storage at room temperature for 6 months. Chocolate containing LP-LRCC5193 can thus be considered a promising probiotic delivery system.

Beneficial effects of extracellular polysaccharide from Rhizopus nigricans on the intestinal immunity of colorectal cancer mice

An extracellular polysaccharide (EPS1-1) extracted from the fermentation broth of Rhizopus nigricans has been proved to enhance the immunity of immunosuppressed mice. The purpose of this study was to investigate the beneficial effects of EPS1-1 on the intestinal immunity of mice with colorectal cancer induced by azoxymethane (AOM) and dextran sodium sulfate (DSS). The results showed that EPS1-1 could resist hydrolysis in an artificial stomach. Oral EPS1-1 modulated gut microbiota and increased the concentration of total short-chain fatty acids (SCFAs) in the feces of colorectal cancer mice compared with the AOM/DSS only-treated mice. Furthermore, EPS1-1 increased the villus length, ratio of villus length and crypt depth in colonic tissues, and improved the number of acid mucus-secreting goblet cells in mice with colorectal cancer. These findings suggest that EPS1-1 might play an important role in the improvement of intestinal function in mice with colorectal cancer, which indicate its strong potential as efficient bio-secure immunotherapy for clinical applications or adjuvant drug.