Gastric pH Conditions Research Articles

Carbon Dot Cross-Linked Gelatin Nanocomposite Hydrogel for pH-Sensing and pH-Responsive Drug Delivery.

Delivery of therapeutics to the intestinal region bypassing the harsh acidic environment of the stomach has long been a research focus. On the other hand, monitoring a system's pH during drug delivery is a crucial diagnosis factor as the activity and release rate of many therapeutics depend on it. This study answered both of these issues by fabricating a novel nanocomposite hydrogel for intestinal drug delivery and near-neutral pH sensing at the same time. Gelatin nanocomposites (GNCs) with varying concentrations of carbon dots (CDs) were fabricated through simple solvent casting methods. Here, CDs served a dual role and simultaneously acted as a cross-linker and chromophore, which reduced the usage of toxic cross-linkers. The proposed GNC hydrogel sample acted as an excellent pH sensor in the near-neutral pH range and could be useful for quantitative pH measurement. A model antibacterial drug (cefadroxil) was used for the in vitro drug release study at gastric pH (1.2) and intestinal pH (7.4) conditions. A moderate and sustained drug release profile was noticed at pH 7.4 in comparison to the acidic medium over a 24 h study. The drug release profile revealed that the pH of the release medium and the percentage of CDs cross-linking influenced the drug release rate. Release data were compared with different empirical equations for the evaluation of drug release kinetics and found good agreement with the Higuchi model. The antibacterial activity of cefadroxil was assessed by the broth microdilution method and found to be retained and not hindered by the drug entrapment procedure. The cell viability assay showed that all of the hydrogel samples, including the drug-loaded GNC hydrogel, offered acceptable cytocompatibility and nontoxicity. All of these observations illustrated that GNC hydrogel could act as an ideal pH-monitoring and oral drug delivery system in near-neutral pH at the same time.

An enteric polymer mitigates the effects of gastric pH on oral absorption of poorly soluble weak acid drugs from supersaturable formulations: A case study with dantrolene

This study demonstrated that an enteric polymer can mitigate the effects of gastric pH on the oral absorption of a poorly water-soluble weak acid drug, dantrolene (DNT). An amorphous solid dispersion (ASD) of DNT with hydroxypropyl methylcellulose (HPMC) acetate succinate (ASD-HPMCAS) was prepared as the enteric released ASD (ER-SF). ASD with HPMC (ASD-HPMC) and DNT sodium salt were also used as immediate-release supersaturable formulations (IR-SFs) with and without water-soluble polymer, respectively. In vivo study with rats and in vitro study with a dissolution/permeation (D/P) system were performed to evaluate oral DNT absorption from each formulation under normal and high gastric pH conditions in rats and humans, respectively. The oral absorption of DNT from both IR-SFs in rats with a high gastric pH was significantly higher than that in rats with a normal gastric pH. In contrast, ASD-HPMCAS attenuated the difference in oral absorption between normal and high gastric pH conditions with significant improvement of DNT absorption. In vivo results implied that an enteric polymer delayed the onset of dissolution until after gastric emptying. ASD-HPMCAS generated supersaturation in the small intestine irrespective of gastric conditions, which was supported bythe in vitrostudy using the D/P system. This study suggested that an enteric polymer is useful to mitigate the inter- and intra-individual differences in oral absorption of poorly water-soluble weak acid drugs.

Interplay of Adsorption, Supersaturation and the Presence of an Absorptive Sink on Drug Release from Mesoporous Silica-Based Formulations.

Mesoporous silica-based formulations of poorly soluble drugs may exhibit incomplete drug release due to drug remaining adsorbed on the silica surface. The goal of this study was (1) to evaluate the adsorption tendency of atazanavir from aqueous solution onto mesoporous silica (SBA-15) and (2) to determine if the drug release from mesoporous silica formulations was promoted by the presence of an absorptive compartment during dissolution testing. Atazanavir (ATZ) formulations with different drug loadings were prepared by incipient impregnation. The solid-state properties of the formulations were analyzed by X-ray diffraction (XRD), differential scanning calorimetry (DSC), infrared spectroscopy and thermogravimetric analysis. Drug release was compared for closed compartment versus absorptive dissolution testing at gastric and intestinal pH. XRD and DSC showed that all formulations were amorphous. Infrared spectra indicated intermolecular interactions between silanol groups in SBA-15 and carbonyl groups in atazanavir. Nanoconfinement of drug in silica mesopores was suggested by thermal analysis. Closed compartment dissolution testing showed incomplete drug release, largely due to theadsorption tendency of ATZ. However, coupled dissolution-absorption studies showed complete release over a 240min time period. This suggested that the depletion of drug in the dissolution medium due to drug diffusion across the membrane promotes drug release. Drug release was further improved when the formulation was first added to fasted state gastric pH conditions followed by pH-shift to intestinal conditions, which was attributed to the higher solubility of atazanavir at low pH. However, ATZ mesoporous silica formulations showed a poorer overall absorption behavior relative to a polymer-based amorphous solid dispersion formulation. This study highlights that absorptive dissolutionconditions promote drug desorption from the silica surface and hence, enhance drug release. Further, the influence of solution pH on drug release underscores the need to consider how variations in physiological conditions may impact the performance of mesoporous silica-based formulations. Graphical Abstract Drug release and adsorption tendency in the absence and presence of an absorptive sink during dissolution testing.

Determination and evaluation of in vitro bioaccessibility of added vitamin C in commercially available fruit-, vegetable-, and cereal-based baby foods.

Knowing the bioaccessibility of vitamin C in foodstuffs produced for infants and young children is necessary to determine their daily vitamin C intake. The purpose of the present study was to investigate the bioaccessibility of vitamin C in fruit-, vegetable-, and cereal-based baby foodstuffs by an in vitro digestion model at varying gastric pHs. The concentrations of measured vitamin C were higher than the declared amounts on their label. The bioaccessibility of vitamin C ranged from 10.4 to 43.4%, and from 0.4 to 19.2% in fruit- and vegetable-based baby foodstuffs (declared vitamin C fortified) at gastric pH 1.5 and 4, respectively. For cereal-based baby foodstuffs, the bioaccessibility ranged from 1.3 to 53.8%, and from 0.3 to 26.3% at gastric pH 1.5 and 4, respectively. As revealed in this research, the bioaccessibility of vitamin C in baby foodstuffs is very low in both gastric pH conditions.

Enhanced Oral Bioavailability and Anti-Echinococcosis Efficacy of Albendazole Achieved by Optimizing the "Spring" and "Parachute".

Maximizing the pharmacological efficacy of albendazole (ABZ), an anti-echinococcosis drug, is essential in the long-term treatment of patients with echinococcosis. As a weakly alkaline drug, ABZ has a pH-dependent solubility that decreases dramatically from gastric fluid (pH 1.4) to intestinal fluid (pH 6.5), where it is absorbed. In this study, we endeavored to develop an optimized tablet formulation of ABZ to improve its dissolution and oral bioavailability from two aspects: a faster initial dissolution in the gastric pH condition (i.e., the "spring") and a more prolonged drug supersaturation in the intestinal pH condition (i.e., the "parachute"). To achieve this goal, ABZ-HCl salt was selected first, which demonstrated a higher intrinsic dissolution rate under pH 1.4 compared with the ABZ free base that is used in the commercial product Albenda. Second, by comparing the ABZ supersaturation kinetics under pH 6.5 in the presence of various polymers including poly(vinylpyrrolidone) (PVP), PVP/VA, hydroxypropyl methylcellulose (HPMC), and HPMC acetate succinate (HPMC-AS), HPMC-AS was found to be the most effective crystallization inhibitor for ABZ, likely due to the hydrophobic interaction between ABZ and HPMC-AS in an aqueous environment. The newly designed tablet formulation containing ABZ-HCl and HPMC-AS showed ∼3 times higher oral bioavailability compared with that of Albenda in Beagle dogs. More significantly, the anti-echinococcosis efficacy of the improved formulation was 2.4 times higher than that of Albenda in a secondary hepatic alveolar echinococcosis Sprague-Dawley rat model. The strategy of simultaneously improving the spring and parachute of an oral formulation of ABZ, by using a highly soluble salt and an effective polymeric crystallization inhibitor, was once again proven to be a viable and readily translatable approach to optimize the unsatisfactory oral medicines due to solubility and bioavailability limitations.

In vitro digestibility of gellan gels loaded with jabuticaba extract: Effect of matrix-bioactive interaction.

Jabuticaba is a native Brazilian fruit rich in phenolic compounds as anthocyanins, showing several benefits for human health but a high sensibility to physicochemical digestion conditions. Gellan is a biopolymer that could be used as a material to protect and carry bioactive compounds, since this polysaccharide is resistant to gastric pH conditions. In this context, gellan gels containing jabuticaba extract were produced using two different ionic strength values (adding calcium ions), which resulted in varied structures. These gels were subjected to two different in vitro digestion processes, modifying the type of mechanical forces applied to simulate stomach and intestine movement conditions. Anthocyanins release (by pH differential method), mechanical properties, confocal and light microscopy of gels were evaluated during in vitro digestibility. Results showed that jabuticaba extract exerted effect on gels mechanical-structural properties, since an increase of stress at rupture (hardness) and a decrease of strain at rupture (deformability) were observed only in gels without calcium addition. Although all gellan gels have improved anthocyanins retention during simulated gastrointestinal digestion process, gels without calcium were more efficient. Our results demonstrated that gellan gels could act as good carriers for anthocyanins, but their efficiency is dependent on the matrix composition, demonstrating that specific studies should be accomplished to determine which changes may occur in the matrix after bioactive addition. Furthermore, our results showed that the type of mechanical forces applied during in vitro digestion is an important variable, since the use of compression (a more similar-to-in vivo system) rather than shear forces increased the release of anthocyanins.

Calcium alginate beads loaded with Mg(OH)2 improve L. casei viability under simulated gastric condition

Alginate beads are commonly used for protection of probiotics against adverse environmental conditions. However, alginate beads are unable to provide complete cell viability under stringent gastric pH conditions. This work considered the incorporation of Mg(OH)2 particles in the formulation of alginate beads to enhance the viability of L. casei under gastric conditions. To this end, alginic acid solution (0.5 g/100 g) was added with different concentrations (0.0, 0.05, 0.1, 0.2 and 0.4 g/100 g alginate) of Mg(OH)2 and a cell load of 10.56 ± 0.1 log CFU/g of L. casei. The beads were formed by dripping one part of the respective former suspensions into ten parts of 0.68 mol/L CaCl2 solution. SEM analysis showed that L. casei cells were effectively entrapped in the beads. FTIR analysis indicated that high Mg(OH)2 concentrations induced unfolding of cell proteins risking the viability of the probiotics. The latter suggests that while Mg(OH)2 is able to increase the pH within the beads respect the pH of the external environment, a suitable concentration should be determined where protein unfolding is reduced or hindered. L. casei viability analysis showed that a concentration of about 0.1 g Mg(OH)2/100 g alginate maximized the cell count under simulated gastric condition.

Pea Ferritin Stability under Gastric pH Conditions Determines the Mechanism of Iron Uptake in Caco-2 Cells

BackgroundIron deficiency is an enduring global health problem that requires new remedial approaches. Iron absorption from soybean-derived ferritin, an ∼550-kDa iron storage protein, is comparable to bioavailable ferrous sulfate (FeSO4). However, the absorption of ferritin is reported to involve an endocytic mechanism, independent of divalent metal ion transporter 1 (DMT-1), the transporter for nonheme iron.ObjectiveOur overall aim was to examine the potential of purified ferritin from peas (Pisum sativum) as a food supplement by measuring its stability under gastric pH treatment and the mechanisms of iron uptake into Caco-2 cells.MethodsCaco-2 cells were treated with native or gastric pH–treated pea ferritin in combination with dietary modulators of nonheme iron uptake, small interfering RNA targeting DMT-1, or chemical inhibitors of endocytosis. Cellular ferritin formation, a surrogate measure of iron uptake, and internalization of pea ferritin with the use of specific antibodies were measured. The production of reactive oxygen species (ROS) in response to equimolar concentrations of native pea ferritin and FeSO4 was also compared.ResultsPea ferritin exposed to gastric pH treatment was degraded, and the released iron was transported into Caco-2 cells by DMT-1. Inhibitors of DMT-1 and nonheme iron absorption reduced iron uptake by 26–40%. Conversely, in the absence of gastric pH treatment, the iron uptake of native pea ferritin was unaffected by inhibitors of nonheme iron absorption, and the protein was observed to be internalized in Caco-2 cells. Chlorpromazine (clathrin-mediated endocytosis inhibitor) reduced the native pea ferritin content within cells by ∼30%, which confirmed that the native pea ferritin was transported into cells via a clathrin-mediated endocytic pathway. In addition, 60% less ROS production resulted from native pea ferritin in comparison to FeSO4.ConclusionWith consideration that nonheme dietary inhibitors display no effect on iron uptake and the low oxidative potential relative to FeSO4, intact pea ferritin appears to be a promising iron supplement.

Gelatin/Maltodextrin Water-in-Water (W/W) Emulsions for the Preparation of Cross-Linked Enzyme-Loaded Microgels.

Cross-linked gelatin microgels were formed in gelatin-in-maltodextrin water-in-water (W/W) emulsions and evaluated as carriers of the enzyme β-galactosidase (β-Gal). The phase behavior of aqueous gelatin/maltodextrin mixtures was studied in detail, focusing on the multiphase region of the phase diagram that is constituted by three equilibrium phases: two immiscible aqueous phases plus one solid phase. The solid phase was analyzed by Raman spectroscopy, and water-in-water emulsions were formed within the multiphase region. Gelation of the dispersed gelatin droplets was induced by cooling and cross-linking with genipin, which is a natural cross-linking reagent of low toxicity, leading to the formation of gelatin microgel particles. These microgels were studied as delivery vehicles for the enzyme lactase, used as a model active component. Various incorporation methods of the enzyme were tested, to achieve highest encapsulation yield and activity recovery. Microgel particles, loaded with the enzyme, can be freeze-dried, and the enzyme remained active after a complete cycle of freeze-drying and rehydration. The stability of the enzyme at 37 °C under gastric and neutral pH conditions was tested and led to the conclusion that the cross-linked microgels could be suitable for use in food-industry, where β-Gal carriers are of interest for hydrolyzing lactose in milk products.

Stabilization Mechanism of Roxithromycin Tablets Under Gastric pH Conditions

Macrolide antibiotics are widely used at clinical sites. Clarithromycin (CAM), a 14-membered macrolide antibiotic, was reported to gelate under acidic conditions. Gelation allows oral administration of acid-sensitive CAM without enteric coating by hindering the penetration of gastric fluid into CAM tablets. However, it is unknown whether this phenomenon occurs in other macrolide antibiotics. In this study, we examined the gelation ability of 3 widely used macrolide antibiotics, roxithromycin (RXM), erythromycin A, and azithromycin. The results indicated that not only CAM but also RXM gelated under acidic conditions. Erythromycin A and azithromycin did not gelate under the same conditions. Gelation of RXM delayed the disintegration of the tablet and release of RXM from the tablet. Disintegration and release were also delayed in commercial RXM tablets containing disintegrants. This study showed that 2 of the 4 macrolides gelated, which affects tablet disintegration and dissolution and suggests that this phenomenon might also occur in other macrolides.

Exogenous enzymes in aquaculture: Alginate and alginate-bentonite microcapsules for the intestinal delivery of shrimp proteases to Nile tilapia

Shrimp processing waste holds digestive proteases with a great potential to be used as feed supplement for Nile tilapia Oreochromis niloticus. In the present work, we characterize both sodium alginate (A) and sodium alginate-bentonite (AB) microcapsules to entrap enzymes obtained from Pleoticus muelleri processing waste. Also, we evaluate these encapsulation methods as a strategy to improve intestinal delivery of exogenous enzymes in O. niloticus in order to enhance their digestion process. The effects of different storage methods, in vitro simulation of gastric pH conditions and exposition to 40 °C were studied. In order to evaluate if microencapsulated shrimp enzymes are active when they reach fish gut, animals were exposed to three treatments: (1) fast, (2) diet and, (3) AB capsules + diet. Alginate capsules were more affected by different storage methods than alginate-bentonite ones. SEM images showed a correlation between decreased enzyme activity and capsule microstructure changes. The best method to store the AB beads is at −20 °C. After incubating for 7 h at 40 °C, we observed a notorious reduction in the enzyme activities of both microcapsules. On the other hand, at pH 3 both microcapsules prevented enzyme irreversible denaturalization and kept 100% of their activity. The overall results indicate that AB capsules are better vehicles to deliver shrimp enzymes in Nile tilapia. In the bioassay, we observed that when fish were fed with treatment 3, the alkaline protease activity in their intestines was 27% higher than that of the diet fish group. Thus, encapsulated shrimp enzymes have a great potential to be used as a feed supplement in fish nutrition. Further trials involving grow bioassays are needed to verify if this shrimp enzyme contained in AB capsules improve fish digestion, feed conversion, body weight and survival rate.

The effect of centrifugation speed and Chitosan-Sodium Tripolyphosphate ratio toward the nanoencapsulation of Sambiloto (Andrographis paniculata) for the formulation of Hepatitis B drug

Hepatits B is a viral infection which attack the liver. One of the compound that can overcome and inhibits Hepatitis B is Andrographolide. The compound was derived from Sambiloto plants (Andrographis paniculate). Andrographolide compound works by inhibiting α-glucosidase which assists the secretion of Hepatitis B virus. The goal of this research is to make nanoencapsulation of sambiloto leaf extracts that was encapsulated in chitosan and STPP. The nanoencapsulation will increase the bioavailability of the body for the administered Andrographolide. The size of the resulting particle at a variation of centrifugal speed of 8.000 RPM with the concentration ratio of chitosan : STPP equals to 0.2%:0.1% (g/mL), was 68.3nm. The loading capacity of the nanoparticles is 67.20% and the encapsulation efficiency of the nanoparticles is 99.48%. The release profile has a cumulative release of 34.55% with slow release in gastric pH conditions and followed by a burst release in intestine pH conditions.

Relationship between gastric pH and plasma concentrations of gefitinib, erlotinib and osimertinib after oral administrations in rat

Back ground: Gefitinib (Gef), erlotinib (Erl) and osimertinib (Osi), the epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs), are recommended as a first-line therapy for non-squamous lung cancer harboring EGFR mutations. Although drug interactions between EGFR-TKIs and gastric acid-suppressing medications are considered clinically significant, there is limited data regarding the influence of various gastric pH conditions on the pharmacokinetics of EGFR-TKIs. The aim of this study were to clarify the relationship between gastric pH and plasma concentrations of the EGFR-TKIs after oral administrations. We evaluated the pharmacokinetics of Gef, Erl and Osi in rats, due to the changes in gastric pH after administration of omeprazole (Ome) or vonoprazan (Von).

Changes in gefitinib, erlotinib and osimertinib pharmacokinetics under various gastric pH levels following oral administration of omeprazole and vonoprazan in rats

1. Although drug interactions between epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and gastric acid-suppressing medications (AS) are considered clinically significant, there is limited data regarding the influence of various gastric pH conditions on the pharmacokinetics of EGFR-TKIs. We aimed to clarify the changes in the pharmacokinetics of the EGFR-TKIs, gefitinib, erlotinib and osimertinib, due to the changes in gastric pH after administration of omeprazole or vonoprazan.2. Omeprazole (10−100 mg/kg, p.o.) and vonoprazan (1−5 mg/kg, p.o.) led to a significant and dose-dependent increase in gastric pH.3. AUC0–3 of gefitinib and erlotinib (5 mg/kg, p.o.) started to decrease at gastric pH 3.3 and 5.6, respectively, reached a plateau at pH > 6, and then significantly decreased up to 47 and 59% of control levels, respectively. AUC0–3 of osimertinib (5 mg/kg, p.o.) was not significantly changed by omeprazole and vonoprazan.4. Although there are some issues regarding the extrapolation of the results of our rat study to humans, careful monitoring of patients treated with gefitinib and erlotinib is needed in cases in which the gastric pH increases from 3 to 5 and especially when the gastric pH is >5 in patients who are co-administered both the EGFR-TKIs and AS.

In Vivo Dissolution and Systemic Absorption of Immediate Release Ibuprofen in Human Gastrointestinal Tract under Fed and Fasted Conditions

In vivo drug dissolution in the gastrointestinal (GI) tract is largely unmeasured. The purpose of this clinical study was to evaluate the in vivo drug dissolution and systemic absorption of the BCS class IIa drug ibuprofen under fed and fasted conditions by direct sampling of stomach and small intestinal luminal content. Expanding current knowledge of drug dissolution in vivo will help to establish physiologically relevant in vitro models predictive of drug dissolution. A multilumen GI catheter was orally inserted into the GI tract of healthy human subjects. Subjects received a single oral dose of ibuprofen (800 mg tablet) with 250 mL of water under fasting and fed conditions. The GI catheter facilitated collection of GI fluid from the stomach, duodenum, and jejunum. Ibuprofen concentration in GI fluid supernatant and plasma was determined by LC-MS/MS. A total of 23 subjects completed the study, with 11 subjects returning for an additional study visit (a total of 34 completed study visits). The subjects were primarily white (61%) and male (65%) with an average age of 30 years. The subjects had a median [min, max] weight of 79 [52, 123] kg and body mass index of 25.7 [19.4, 37.7] kg/m2. Ibuprofen plasma levels were higher under fasted conditions and remained detectable for 28 h under both conditions. The AUC0-24 and Cmax were lower in fed subjects vs fasted subjects, and Tmax was delayed in fed subjects vs fasted subjects. Ibuprofen was detected immediately after ingestion in the stomach under fasting and fed conditions until 7 h after dosing. Higher levels of ibuprofen were detected in the small intestine soon after dosing in fasted subjects compared to fed. In contrast to plasma drug concentration, overall gastric concentrations remained higher under fed conditions due to increased gastric pH vs fasting condition. The gastric pH increased to near neutrality after feedingbefore decreasing to acidic levels after 7 h. Induction of the fed state reduced systemic levels but increased gastric levels of ibuprofen, which suggest that slow gastric emptying and transit dominate the effect for plasma drug concentration. The finding of high levels of ibuprofen in stomach and small intestine 7 h post dosing was unexpected. Future work is needed to better understand the role of various GI parameters, such as motility and gastric emptying, on systemic ibuprofen levels in order to improve in vitro predictive models.

Release Profile of Andrographis paniculata Leaf Extract Nanocapsule as α-Glucosidase Inhibitors

Andrographis paniculata is one of 13 leading commodities Indonesian medicinal plants through the Ditjen POM. Andrographolide as main active compound has been shown to have many pharmacological activities, one of which is as α-glucosidase enzyme inhibitors which has clinical potential as an antitumor, antiviral, antidiabetic, and immunoregulator agents. This study aims to do nanoencapsulation of Andrographis paniculatar leaf extract to increase its active compound bioavailability and get a release profile through synthetic fluids media simulation. Nanoencapsulation with ionic gelation method result the encapsulation efficiency and loading capacity values of 73.47% and 46.29% at 2%: 1% of chitosan: STPP ratio. The maximum α-glucosidase inhibition of 37.17% was obtained at 16% concentration. Burst release at gastric pH conditions indicate that most of the drug (in this study is an Andrographis paniculata leaf extract) adsorbed on the surface of the nanoparticles an indicates that the kind of nanoparticle formed is nanosphere.

Lactoferrin: A Powerful Antimicrobial Protein Present in Milk

Lactoferrin (Lf) is an iron-chelating glycoprotein present in milk and mucosal secretions, a component of the mammalian innate immune system. Lf is microbiostatic and microbicidal. Lf can reduce the bacterial expression of virulence factors, such as those involved in biofilm production and protease secretion. The high identity among mammalian Lf sequences facilitates its use in human and veterinary medicine. Lf of bovine origin is the principal Lf used due to its commercial availability through purification from milk whey; recombinant Lfs (bovine, human, and porcine) have been used as well. Lf is a stable protein that retains its physicochemical characteristics under gastric pH conditions, and in most cases it is bioactive even after digestion; thus, the incorporation of Lf into diets facilitates its administration to animals. The aim of this review is to examine original research in which the effects of bovine and porcine Lf on pathogens of domestic animals have been demonstrated through in vitro and in vivo assays, with the purpose of ascertaining the benefits that Lf provides in the treatment of infectious diseases.

Modelling of tetracycline resistance gene transfer by commensal Escherichia coli food isolates that survived in gastric fluid conditions

Antimicrobial resistance (AR) is a major public health concern and a food safety issue worldwide. Escherichia coli strains, indicators of antibiotic resistance, are a source of horizontal gene transfer to other bacteria in the human intestinal system. A probabilistic exposure model was used to estimate the transfer of the AR gene tet(A). The acid resistance and kinetic behaviour of E. coli was analysed as a function of pH to describe the inactivation of E. coli in simulated gastric fluid (SGF), the major host barrier against exogenous micro-organisms. The kinetic parameters of microbial inactivation in SGF were estimated using GInaFiT, and log-linear + tail and Weibull models were found to be suitable for commensal and enterohaemorrhagic E. coli (EHEC), respectively. A probabilistic exposure model was developed to estimate E. coli survival in gastric pH conditions as well as gene transfer from resistant to susceptible cells in humans. E. coli-contaminated retail foods for consumption without further cooking and gastric pH data in South Korea were considered as an example. The model predicts that 22–33% of commensal E. coli can survive under gastric pH conditions of Koreans. The estimated total mean tet(A) transfer level by commensal E. coli was 1.68 × 10–4–8.15 × 10–4 log CFU/mL/h. The inactivation kinetic parameters of E. coli in SGF and the quantitative exposure model can provide useful information regarding risk management options to control the spread of AR.

СУЧАСНИЙ СТАН СТВОРЕННЯ, ВИРОБНИЦТВА ТА ДОСЛІДЖЕННЯ ТАБЛЕТОВАНИХ ЛІКАРСЬКИХ ПРЕПАРАТІВ. Повідомлення 24. Осмотичні системи вивільнення та доставки лікарських речовин: розробка, характеристика та їх класифікація

Проведено огляд літературних джерел щодо розробки та дослідження осмотичних систем вивільнення та доставки лікарських речовин

Development of pH-Independent Drug Release Formulation Using Lipocalin-Type Prostaglandin D Synthase

The purpose of this study was to develop a pH-independent drug release formulation using lipocalin-type prostaglandin D synthase, a member of the lipocalin superfamily, with the function of forming complexes together with various small lipophilic molecules. Dipyridamole, a poorly water-soluble drug, showing a pH-dependent solubility profile, was used as the model drug. The solubilization of dipyridamole was achieved by a simple complex formulation method with lipocalin-type prostaglandin D synthase. The complex formulation was produced successfully by spray drying, and the obtained powder formulation showed complete dissolution in fasted-state simulated gastric fluid (pH, 1.6) and phosphate-buffered solution (pH, 6.8). In addition, the potential stability of the complex formulation was assessed, and the dissolution profile of the produced powder at pH 6.8 was maintained after 4-week storage under several storage conditions. Furthermore, a pharmacokinetic study using hypochlorhydria model rats was performed to verify the improvement of the intestinal absorption behavior, and eventually the complex formulation overcame the problematic absorption profile of dipyridamole in the elevated gastric pH conditions. These results, taken together, demonstrate that the use of this well-designed drug-delivery carrier is feasible for the development of pH-independent drug release formulations.