Search Results (29)

Background: Agarwood has been widely used for the treatment of gastrointestinal diseases. Our research group has suggested that agarwood alcohol extracts (AAEs) provide good gastric mucosal protection. However, the exact mechanisms underlying this effect remain unclear. Objectives: This study aimed to investigate the ameliorative effect of agarwood chromone on gastric ulcers and its mechanism. Methods: Network pharmacology was used to predict the disease spectrum and key therapeutic targets of 2-(2-phenylethyl)chromone (CHR1) and 2-(2-(4-methoxyphenyI)ethyl)chromone (CHR2). Mice were orally administered CHR1 (20 and 40 mg/kg) and CHR2 (20 and 40 mg/kg) and the positive drug omeprazole as an enteric-coated capsule (OEC, 40 mg/kg) orally. After 7 days of pretreatment with the CHRs, gastric ulcers were induced using absolute ethanol (0.15 mL/10 g). The ulcer index, gastric histopathology, biochemical parameters, and inflammatory and apoptotic proteins were evaluated. Finally, binding of the core compounds to the key targets was verified via molecular docking and visualized. Results: The pharmacological results show that the CHRs reduced the gastric occurrence and ulcer inhibition rates by up to more than 70% in a dose-dependent manner. The CHRs decreased the levels of interleukin 6 (IL-6), interleukin 12 (IL-12), interleukin 18 (IL-18), and tumor necrosis factor α (TNF-α), and improved the severity of the pathological lesions in the gastric tissue. The expression of ATP-binding box transporter B1 (ABCB1), arachidonic acid-5-lipoxygenase (ALOX5), nuclear factor kappa B (NF-κB), cysteinyl aspartate specific proteinase 3 3 (Caspase3), and cysteinyl aspartate specific proteinase 9 (Caspase9) was inhibited, but the expression of B-cell lymphoma-2 (Bcl-2) was enhanced. The CHRs bound stably to the key targets via hydrogen bonding, van der Waals forces, etc. These results demonstrate that agarwood chromone compounds exert alleviative effects against the occurrence and development of gastric ulcers by inhibiting the NF-κB and caspase pathways. The CHRs have a therapeutic effect on gastric ulcers through anti-inflammation and anti-apoptosis mechanisms. Conclusions: This study suggests that agarwood may have a potential role in drug development and the prevention and treatment of gastrointestinal inflammation, and tumors. Full article

Introduction. The rise of multidrug resistance in Gram-negative ESKAPE pathogens is a critical challenge for modern healthcare. Colistin (CT), a peptide antibiotic, remains a last-resort treatment for infections caused by these superbugs due to its potent activity against Gram-negative bacteria and the rarity of resistance. However, its clinical use is severely limited by high nephro- and neurotoxicity, low oral bioavailability, and other adverse effects. A promising strategy to improve the biopharmaceutical properties and safety profile of antibiotics is the development of biopolymer-based delivery systems, also known as nanoantibiotics. Objective. The aim of this study was to develop polyelectrolyte complexes (PECs) for the oral delivery of CT to overcome its major limitations, such as poor bioavailability and toxicity. Methods. PECs were formulated using chondroitin sulfate (CHS) and a cyanocobalamin–chitosan conjugate (CSB12). Vitamin B12 was incorporated as a targeting ligand to enhance intestinal permeability through receptor-mediated transport. The resulting complexes (CHS-CT-CSB12) were characterized for particle size, ζ-potential, encapsulation efficiency, and drug release profile under simulated gastrointestinal conditions (pH 1.6, 6.5, and 7.4). The antimicrobial activity of the encapsulated CT was evaluated in vitro against Pseudomonas aeruginosa. Results. The CHS-CT-CSB12 PECs exhibited a hydrodynamic diameter of 446 nm and a ζ-potential of +28.2 mV. The encapsulation efficiency of CT reached 100% at a drug loading of 200 µg/mg. In vitro release studies showed that approximately 70% of the drug was released within 1 h at pH 1.6 (simulating gastric conditions), while a cumulative CT release of 80% over 6 h was observed at pH 6.5 and 7.4 (simulating intestinal conditions). This release profile suggests the potential use of enteric-coated capsules or specific administration guidelines, such as taking the drug on an empty stomach with plenty of water. The antimicrobial activity of encapsulated CT against P. aeruginosa was comparable to that of the free drug, with a minimum inhibitory concentration of 1 µg/mL for both. The inclusion of vitamin B12 in the PECs significantly improved intestinal permeability, as evidenced by an apparent permeability coefficient (P_app) of 1.1 × 10⁻⁶ cm/s for CT. Discussion. The developed PECs offer several advantages over conventional CT formulations. The use of vitamin B12 as a targeting ligand enhances drug absorption across the intestinal barrier, potentially increasing oral bioavailability. In addition, the controlled release of CT in the intestinal environment reduces the risk of systemic toxicity, particularly nephro- and neurotoxicity. These findings highlight the potential of CHS-CT-CSB12 PECs as a nanotechnology-based platform for improving the delivery of CT and other challenging antibiotics. Conclusions. This study demonstrates the promising potential of CHS-CT-CSB12 PECs as an innovative oral delivery system for CT that addresses its major limitations and improves its therapeutic efficacy. Future work will focus on in vivo evaluation of the safety and efficacy of the system, as well as exploring its applicability for delivery of other antibiotics with similar challenges. Full article

Background/Objectives: Omeprazole undergoes degradation in acidic conditions, which makes it unstable in low pHs found in the gastric environment. The vast majority of already marketed omeprazole formulations use enteric polymer coatings to protect the drug from exposure to acidic pH in the stomach, allowing for drug release in the small intestine where the pH is higher. This study aimed to explore the technical aspects of using stomach acid neutralizers as an alternative to polymeric coatings for omeprazole. Methods: After evaluating various neutralizers, magnesium oxide and sodium bicarbonate were chosen to be incorporated into capsules containing omeprazole, which then underwent in vitro dissolution testing to assess their ability to maintain optimal pH levels and ensure appropriate dissolution kinetics. Hygroscopicity and chemical stability of the selected formulation were tested to prove pharmaceutical quality of the product. An in vivo pharmacokinetic study was conducted to demonstrate the efficacy of the omeprazole–sodium bicarbonate formulation in providing faster absorption in humans. Results: Sodium bicarbonate was selected as the most suitable antacid for ensuring omeprazole stabilization. Its quantity was optimized to effectively neutralize stomach acid, facilitating the rapid release and absorption of omeprazole. In vitro studies demonstrated the ability of the formulation to neutralize gastric acid within five minutes. In vivo studies indicated that maximum concentrations of omeprazole were achieved within half an hour. The product met the requirements of pharmaceutical quality. Conclusions: An easily manufacturable, fast-absorbing oral formulation was developed as an alternative to enteric-coated omeprazole. Full article

Grouting technology is an important method of ground reinforcement and can effectively improve the stability of engineering rock mass. During overburden isolated grouting in coal mines, the influence of unexpected fractures may lead to substantial grout leakage, resulting in ineffective grouting. The existing natural sedimentation sealing method is mainly applicable to small fractures and low grout flow, while the chemical-reagent rapid-sealing method can cause grouting channel blocking, making it less suitable for overburden isolated grouting. This paper proposes a “capsule” sealing method, detailing the preparation of the sealing material and evaluation of its properties through testing. The sealing material, prepared using the air suspension method, was coated with paraffin on a superabsorbent polymer (SAP) material, which has delayed expansion characteristics. Although this material does not expand within the grouting fractures of overburden rock, it expands rapidly upon entering the leakage channel, accumulating within the channel to achieve effective sealing. A simulation experimental system was designed to simulate the sealing of the slurry leakage channel, and the sealing characteristics were experimentally investigated. Under consistent particle size conditions, a higher film cover ratio led to a more pronounced delayed expansion effect and extended the time required for the sealing material to achieve its maximum expansion. When the content of sealing material with particle sizes of 20 mesh, 40 mesh, and 60 mesh, and a film ratio of 20% was 1.0%, the fractures below 4 mm were effectively sealed. When the fracture aperture is 4–6 mm, the sealing material with a covering ratio of 20% or 30% should have a minimum content of 1.5%, while the sealing material with a covering ratio of 50% should have a minimum content of 2.0%. The findings of this study outline an effective prevention and control method for the sealing of abnormal slurry leakage in overburden isolated grouting engineering. Full article

Background/Objectives: Coated drug pellets enjoy widespread use in hard gelatine capsules. In heterogeneous pellets, the drug substance is layered onto core pellets. Coatings are often applied to generate a retarded release or an enteric coating. Methods: In the present study, the thickness of a polymer coating layer on drug pellets was correlated to the drug release kinetics. Results: The question should be answered whether it is possible to stop the coating process when a layer thickness referring to an intended drug release is achieved. Inert pellets were first coated with sodium benzoate and second with different amounts of water insoluble polyacrylate in a fluidized bed apparatus equipped with a Wurster inlet. The whole process was controlled in-line and at-line with process analytical technology by the measurement of the particle size and the layer thickness. The in-vitro sodium benzoate release was investigated, and the data were linearized by different standard models and compared with the polyacrylate layer thickness. With increasing polyacrylate layer thickness the release rate diminishes. The superposition of several processes influencing the release results in release profiles corresponding approximately to first order kinetics. The coating layer thickness corresponds to a determined drug release profile. Conclusions: The manufacturing of coated drug pellets with intended drug release is possible by coating process control and layer thickness measurement. Preliminary investigations are necessary for different formulations. Full article

Oral vaccines, unlike injected, induce intestinal secretory immunoglobulin A (sIgA) mimicking our natural defense against gut pathogens. We previously observed sIgA responses after administering the Clostridioides difficile colonisation factor CD0873 orally in enteric capsules to hamsters. Enteric-coated capsules are designed to resist dissolution in the stomach and disintegrate only at the higher pH of the small intestine. However, the variable responses between animals led us to speculate suboptimal transit of antigens to the small intestine. The rate of gastric emptying is a controlling factor in the passage of oral drugs for subsequent availability in the small intestine for absorption. Whilst in humans, food delays gastric emptying, in rats, capsules can empty quicker from fed stomachs than from fasted. To test in hamsters if fasting improves the delivery of antigens to the small intestine, as inferred from the immune responses generated, 24 animals were dosed intragastrically with enteric capsules containing recombinant CD0873. Twelve hamsters were fasted for 12 h prior to each dose and the other 12 fed. Significantly higher sIgA titres, with significantly greater bacterial-adherence-blocking activity, were detected in small intestinal lavages in the fasted group. We conclude that fasting in hamsters improves intestinal delivery leading to more robust responses. Full article

The coating process for solid dosage forms is widely used in the pharmaceutical industry but presents challenges for small-scale production, needed in personalized medicine and clinical or galenic settings. This study aimed to evaluate immersion coating, a cost-effective small-scale method, for enteric-coated gelatin capsules using standard equipment. Two enteric coating polymers and different polymer concentrations were tested, along with API solubility. Results were compared with commercially available enteric capsule shells. Successful preparation of enteric coating capsules via immersion necessitates a comprehensive grasp of API and enteric polymer behavior. However, utilizing commercially available enteric capsule shells does not guarantee ease or robustness, as their efficacy hinges on the attributes of the active ingredient and excipients. Notably, coating with Eudragit S100 stands out for its superior process robustness, requiring minimal or no development time, thus representing the best option for small-scale enteric capsule production. Full article

Ingestible self-configurable proximity-enabling devices have been developed as a non-invasive platform to improve the bioavailability of drug compounds via swellable or self-unfolding devices. Self-unfolding foils support unidirectional drug release in close proximity to the intestinal epithelium, the main drug absorption site following oral administration. The foils are loaded with a solid-state formulation containing the active pharmaceutical ingredient and then coated and rolled into enteric capsules. The coated lid must remain intact to ensure drug protection in the rolled state until targeted release in the small intestine after capsule disintegration. Despite promising results in previous studies, the deposition of an enteric top coating that remains intact after rolling is still challenging. In this study, we compare different mixtures of enteric polymers and a plasticizer, PEG 6000, as potential coating materials. We evaluate mechanical properties as well as drug protection and targeted release in gastric and intestinal media, respectively. Commercially available Eudragit^® FL30D-55 appears to be the most suitable material due to its high strain at failure and integrity after capsule fitting. In vitro studies of coated foils in gastric and intestinal media confirm successful pH-triggered drug release. This indicates the potential advantage of the selected material in the development of self-unfolding foils for oral drug delivery. Full article

Developing delayed-release formulations for acid-sensitive actives can be a costly and time-consuming process. However, ready-to-fill functional capsules, such as EUDRACAP^® can significantly mitigate these challenges. The in vitro performance of EUDRACAP^® enteric was evaluated in two typical delayed-release scenarios: for diclofenac (a drug that can cause irritation to gastric mucosa), and for omeprazole (a drug susceptible to degradation due to the acidity of gastric fluid). The prototypes were tested in HCl 0.1N according to the USP <711> for at least 2 h and compared to commercial products. The results showed that the performance of EUDRACAP^® was below LOD and in compliance with the requirements for drug release in acidic media (NMT 10%). Additionally, the impurities were evaluated after the acidic stress. The low total percentage of impurities of 0.44% for diclofenac (NMT 1.50%) and 0.22% for omeprazole (NMT 2.00%) indicates a very good protection by EUDRACAP^®. A comprehensive comparative analysis of the in vitro performance clearly showed the acid protection capability of EUDRACAP^® enteric capsules making them a serious alternative to existing enteric dosage forms alternatives. EUDRACAP^® is an accessible solution both in large-scale industrial and smaller pharmacy settings. Offering increased accessibility, affordability, and convenience to manufacturers and consumers alike and leading to improved healthcare outcomes. Full article

In this study, we developed a tamsulosin pellet-loaded orally disintegrating tablet (ODT) that is bioequivalent to commercially available products and has improved patient compliance using microcrystalline cellulose (MCC) and mannitol. Utilizing the fluid bed technique, the drug, sustained release (SR) layer, and enteric layer were sequentially prepared by coating MCC pellets with the drug, HPMC, Kollicoat, and a mixture of Eudragit L and Eudragit NE, respectively, resulting in the production of tamsulosin pellets. The tamsulosin pellet, composed of the MCC pellet, drug layer, SR layer, and enteric layer at a weight ratio of 20:0.8:4.95:6.41, was selected because its dissolution was equivalent to that of the commercial capsule. Tamsulosin pellet-loaded ODTs were prepared using tamsulosin pellets and various co-processed excipients. The tamsulosin pellet-loaded ODT composed of tamsulosin pellets, mannitol–MCC mixture, silicon dioxide, and magnesium stearate at a weight ratio of 32.16:161.84:4.0:2.0 gave the best protective effect on the coating process and a dissolution profile similar to that of the commercial capsule. Finally, no significant differences in beagle dogs were observed in pharmacokinetic parameters, suggesting that they were bioequivalent. In conclusion, tamsulosin pellet-loaded ODTs could be a potential alternative to commercial capsules, improving patient compliance. Full article

Bioavailability refers to a fraction of a substance that is potentially absorbed from the gastrointestinal tract and enters the systemic circulation (blood). This term is related to various substances, including minerals, that are present in a complex matrix of food which is consumed every day as natural products and pharmaceutical preparations, e.g., dietary supplements. The purpose of the study was to assess the bioavailability of Se from selected dietary supplements, with the simultaneous assessment of the effect the diet type (standard, basic and high-residue diets) has on relative bioavailability. The research included a two-stage in vitro model of digestion using cellulose dialysis tubes of the food rations with the addition of dietary supplements. Se was determined using the ICP-OES method. The bioavailability of Se from dietary supplements, in the presence of food matrix, was determined to be within the range of 19.31–66.10%. Sodium selenate was characterized by the highest value of this parameter, followed by organic forms and sodium selenite. The basic diet, characterized by moderate protein and high carbohydrate and fiber contents, positively influenced the bioavailability of Se. The bioavailability of Se was also influenced by the pharmaceutical form of the product—the highest was for tablets, followed by capsules and coated tablets. Full article

Current evidence supports the use of extra virgin olive oil (EVOO) and its minor components such as hydroxytyrosol or 3,4-dihydroxyphenyl ethanol (DOPET), to improve cardiovascular and metabolic health. Nevertheless, more intervention studies in humans are needed because some gaps remain in its bioavailability and metabolism. The aim of this study was to investigate the DOPET pharmacokinetics on 20 healthy volunteers by administering a hard enteric-coated capsule containing 7.5 mg of bioactive compound conveyed in EVOO. The treatment was preceded by a washout period with a polyphenol and an alcohol-free diet. Blood and urine samples were collected at baseline and different time points, and free DOPET and metabolites, as well as sulfo- and glucuro-conjugates, were quantified by LC-DAD-ESI-MS/MS analysis. The plasma concentration versus time profiles of free DOPET was analyzed by a non-compartmental approach, and several pharmacokinetic parameters (C_max, T_max, T_1/2, AUC_{0–440 min}, AUC_0–∞, AUC_t–∞, AUC_{extrap_pred}, C_last and K_el) were calculated. Results showed that DOPET C_max (5.5 ng/mL) was reached after 123 min (T_max), with a T_1/2 of 150.53 min. Comparing the data obtained with the literature, the bioavailability of this bioactive compound is about 2.5 times higher, confirming the hypothesis that the pharmaceutical formulation plays a pivotal role in the bioavailability and pharmacokinetics of hydroxytyrosol. Full article

Despite poor absorption properties, delivery to the colon of bioactive compounds administered by the oral route has become a focus of pharmaceutical research over the last few decades. In particular, the high prevalence of Inflammatory Bowel Disease has driven interest because of the need for improved pharmacological treatments, which may provide high local drug concentrations and low systemic exposure. Colonic release has also been explored to deliver orally biologics having gut stability and permeability issues. For colon delivery, various technologies have been proposed, among which time-dependent systems rely on relatively constant small intestine transit time. Drug delivery platforms exploiting this physiological feature provide a lag time programmed to cover the entire small intestine transit and control the onset of release. Functional polymer coatings or capsule plugs are mainly used for this purpose, working through different mechanisms, such as swelling, dissolution/erosion, rupturing and/or increasing permeability, all activated by aqueous fluids. In addition, enteric coating is generally required to protect time-controlled formulations during their stay in the stomach and rule out the influence of variable gastric emptying. In this review, the rationale and main delivery technologies for oral colon delivery based on the time-dependent strategy are presented and discussed. Full article

Niclosamide is an FDA-approved anthelmintic that is being studied in clinical trials as a chemotherapeutic and broad-spectrum antiviral. Additionally, several other applications are currently in the preclinical stage. Unfortunately, niclosamide is a poorly water soluble molecule, with reduced oral bioavailability, which hinders its use for new indications. Moreover, niclosamide is a poor glass former; in other words, the molecule has a high tendency to recrystallize, and it is virtually impossible to generate a stable amorphous solid employing the neat molecule. Previously, our group reported the development of an amorphous solid dispersion (ASD) of niclosamide (niclosamide ASD) that generates nanoparticles during its dissolution, not only increasing niclosamide’s apparent solubility from 6.6 ± 0.4 to 481.7 ± 22.2 µg/mL in fasted state simulated intestinal fluid (FaSSIF) but also its oral bioavailability 2.6-fold in Sprague–Dawley rats after being administered as a suspension. Nevertheless, niclosamide ASD undergoes recrystallization in acidic media, and an enteric oral dosage form is needed for its translation into the clinic. In this work, we further characterized the nanoparticles that generated during the dissolution of the niclosamide ASD. Cryogenic transmission electron microscopy (Cryo-TEM) and wide-angle X-ray scattering (WAXS) revealed that the nanoparticles were amorphous and had a particle size of ~150 nm. The oral dosage forms of niclosamide ASD were formulated using commercial enteric capsules (Capsuline^® and Eudracap^TM) and as enteric-coated tablets. The enteric dosage forms were tested using pH-shift dissolution and acid-uptake tests, using the USP type II dissolution apparatus and the disintegration apparatus, respectively. The capsules exhibited a higher percentage of weight gain, and visual rupture of the Capsuline capsules was observed. Eudracap capsules protected the formulation from the acidic media, but polymer gelling and the formation of a nondispersible plug were noted during dissolution testing. In contrast, enteric-coated tablets protected the formulation from acid ingress and maintained the performance of niclosamide ASD granules during dissolution in FaSSIF media. These enteric-coated tablets were administered to beagle dogs at a niclosamide dose of 75 mg/kg, resulting in plasma concentrations of niclosamide higher than those reported in the literature using solubilized niclosamide at a higher dose (i.e., 100 mg/kg). In summary, an enteric oral dosage form of niclosamide ASD was formulated without hindering the generation of nanoparticles while maintaining the increase in the niclosamide’s apparent solubility. The enteric-coated tablets successfully increased the niclosamide plasma levels in dogs when compared to a niclosamide solution prepared using organic solvents. Full article

Intrinsically, enteric capsule shells offer several advantages compared to coating of dosage forms with enteric polymers. We undertook a systematic investigation to elucidate capsule-fill parameters that may result in premature gastric drug release from Vcaps^® Enteric capsules (Lonza CHI, Morristown, NJ, USA). Four model drugs with different ionization and solubility profiles were investigated: acetaminophen, ketoprofen, trimethoprim and atenolol. Different fill loads, diluents and drug-to-diluent ratios were explored. Enteric capsules were filled with drug or drug and diluent powder mix and underwent USP II dissolution testing using mini-vessels and paddles. Capsules were tested in pH 2 (0.01 M HCl) or pH 4.5 (3.2 × 10⁻⁵ M HCl) 200 mL acid media to simulate normal, fasted or hypochlorhydric gastric pH, respectively. Acetaminophen, trimethoprim and atenolol displayed premature gastric drug release from enteric capsules. The extent of premature release was dependent on drug solubility, ionization profile and capsule-fill level. At 100 mg drug-fill level, acetaminophen, trimethoprim and atenolol gave rise to 10.6, 12.2 and 83.1% drug release, respectively, in normal, fasted, gastric fluids. Diffusion layer pH of trimethoprim and atenolol in pH 2 media was determined to be pH 6.3 and 10.3, respectively. Upon increasing capsule-fill load using microcrystalline cellulose as a diluent, a significant reduction in premature gastric release was observed. However, including mannitol as a diluent was only effective at decreasing premature drug release at a low drug-to-diluent ratio. Systematic in vitro screening of enteric capsule fills needs to be conducted to ensure that drug product performance is not compromised. Full article