The field of oral drug delivery has witnessed significant advancements, with a focus on developing innovative formulations to address challenges associated with traditional dosage forms, especially for patients with difficulties in swallowing. Fast Dissolving Tablets (FDTs) have emerged as a promising class of tablets designed to rapidly disintegrate or dissolve in saliva, providing a convenient and patient-friendly alternative for various populations.
This article explores the unique properties, advantages, and potential applications of FDTs, emphasizing their role in overcoming challenges posed by conventional oral drug delivery systems. FDTs offer rapid dissolution within 15-120 seconds in the buccal cavity, facilitating direct absorption through the buccal mucosa and ensuring quick therapeutic effects. This characteristic proves particularly beneficial for individuals facing swallowing challenges, such as pediatric and geriatric patients, or those with conditions like dysphagia.
Recognizing the significance of FDTs, the European Pharmacopoeia (EP) has officially recognized them as “oral dissolving tablets,” highlighting their acceptance in both academic and industrial settings. The article delves into the anatomical and physiological characteristics of the oral cavity, shedding light on the buccal epithelium, oral mucosa vascularization, and salivary flow, which play crucial roles in drug absorption.
The ideal features of FDTs include rapid dissolution or disintegration, high drug load capacity, masking of bitter taste, positive mouth feel, ease of transport, and reduced sensitivity to environmental factors. The advantages of FDTs extend to their administration for patients unable to swallow, convenient treatment for bedridden and mobile patients, enhanced mouth feel and taste masking, ease of administration, and precise dosing.
Despite their advantages, FDTs come with limitations, including issues related to mechanical strength, hygroscopic nature, brittleness, and challenges with bitter drugs or unpleasant odors. Overcoming these challenges requires a careful formulation approach to balance rapid disintegration with mechanical strength and taste masking.
The article also discusses the salient characteristics of Fast Dissolving Dosage Forms (FDDDS) and various techniques for preparing FDTs, such as freeze-drying, tablet molding, and spray drying. Additionally, it explores the role of non-invasive drug delivery systems in addressing pharmaceutical industry needs, including improving drug half-life, solubility/stability, and bioavailability.
MAOs are flavoenzymes that aid in the oxidative deamination of neurotransmitters such as dopamine, serotonin, and epinephrine. MAO inhibitors are antidepressants that act by inhibiting neurotransmitter breakdown in the brain and controlling mood. MAO inhibitors with the chlorophenyl-chromone-carboxamide structure have been shown in investigations to be extremely effective. The current study employs in-silico screening, MD simulation, and drug kinetics evaluation, all of which are evaluated using different criteria. The study comprised 37 ligands, and three stood out as the best, with greater binding scores above the threshold value. Docking analysis found that compound 34 had the highest docking score in the series (-13.60 kcal/mol) and interacted with the important amino acids TYR 435, CYS 397, CYS 172, PHE 343, TYR 398, and LYS 296 required for MAO inhibitory activity. The ADMET study revealed that the compounds had drug-like properties. The results of this study could be used to develop chromone drugs that target the MAO inhibitor. The top three ligands with the highest force and work were then simulated using molecular dynamics. The protein-ligand complexes had steady trajectories throughout the 100 ns simulation, according to the data. Furthermore, the drug likeliness predicted by ADMET analysis findings indicated that the top three lead compounds had strong inhibitory efficiency, superior pharmacokinetics, and were non-toxic under physiological settings. As a result, these compounds have the potential to be exploited as possible treatment medications for PD.
Background: The COVID-19 pandemic significantly affects patients with RA and other rheumatic diseases. Our study aims to explore the factors associated with COVID-19-related fatality among Rheumatoid Arthritis (RA) patients, especially immunomodulatory therapies, using the international Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS).
Methods: Reportes from FAERS were extracted from February 2020 to September 2022, and uesd for this cross-sectional analysis. The investigative outcome was COVID-19-related death. Age, sex, region, event date, and immunomodulatory medications classies were included as co-variates in multivariable logistic regression. In view of the different targeting and affinity of individual JAKi, Tofacitinib, Upadacitinib and Baricitinib was respectively analyzed.
Results: In all, 3808 cases (mean age 58.85 years, 82.8% female), 267 (7.0%) died. JAKi therapies (41.2%), followed by TNFi (37.7%), IL-1i (12.2%), IL-6i (4.1%) and Anti-CD20 (3%) were reported. Risk factors associated with COVID-19-related death in RA patients were age (odds ratio [OR]: 1.06; 95% confidence interval [CI]: 1.05–1.08; p < 0.01), male sex (1.71, 1.26–2.33; p = 0.01) and anti-CD20 therapies (5.05; 1.40–18.19; p = 0.013). With TNFi conference, anti-CD20 was still a risk predictor (4.29; 2.39–7.70; p < 0.01). Other DMARDs except for anti-CD20, did not confer a significant association with mortality, compared with csDMARDs or TNFi. Individual JAKi showed no obvious difference in the risk of death, compared with csDMARDs or TNFis.
Conclusion: Conclusions Using FAERS open access data for risk prediction of death, anti-CD20 therapies were recognized as a risk factor for COVID-19-related fatalities among RA patients, other immunomodulatory therapies were not associated with mortality, compared with csDMARDs or TNFis.
This study focuses on the development of a liposomal preparation for the targeted delivery of Telmisartan in the context of breast cancer treatment. Telmisartan, a pharmaceutical agent with potential anticancer properties, has been encapsulated within liposomes, lipid-based vesicles known for their capacity to enhance drug delivery and improve therapeutic outcomes. The formulation and characterization of Telmisartan-loaded liposomes were conducted, evaluating factors such as size, shape, and drug release profiles. The findings demonstrate that the liposomal preparation effectively encapsulates Telmisartan, maintaining its pharmacological properties. The development of such liposomal formulations holds promise for advancing breast cancer therapies, offering the potential for enhanced treatment efficacy and reduced side effects. This research contributes to the ongoing efforts to explore innovative drug delivery strategies in the realm of breast cancer treatment. Breast cancer is a pervasive and challenging malignancy affecting women worldwide. In the quest for more effective and targeted treatment approaches, the development of liposomal preparations for delivering therapeutic agents to breast cancer cells has emerged as a promising avenue. Telmisartan, originally recognized for its antihypertensive properties, has been increasingly investigated for its potential anticancer effects. This study delves into the design and evaluation of a liposomal formulation for Telmisartan, aiming to enhance its therapeutic potential in breast cancer. The formulation process involved the encapsulation of Telmisartan within lipid-based liposomes, which are well-known for their ability to carry a variety of drugs, protect them from degradation, and enhance their selective delivery to tumor cells.
The use of in-silico research in drug development is growing. Aspects of drug discovery and development, such as virtual ligand screening and profiling, target and lead finding, and compound library creation, are simulated by computational approaches. Databases, pharmacophores, homology models, quantitative structure–activity connections, machine learning, data mining, network analysis tools, and computer-based data analysis tools are examples of in-silico techniques. These techniques are mostly applied in conjunction with the production of in vitro data to build models that facilitate the identification and refinement of new compounds by providing insight into their features related to absorption, distribution, metabolism, and excretion.
Influenza virus transmission is largely mediated by its mutation and genome reassortment from distinct strains resulting in drug-resistances and pandemics. This necessitates the need for the discovery of more potential influenza inhibitors to prevent future epidemics. An in-silico approach was utilized here to design six new (21a-f) potential inhibitors of influenza neuraminidase (NA) using a hit compound 21 with good binding affinity, predicted activity, and pharmacokinetic properties in our previous work. The modeled activities (pEC50) of the newly designed compounds (ranging between 8.188 and 7.600) were better than that of the hit compound 21 with predicted activity (pEC50) of 6.0101 and zanamivir (pEC50 of 5.6755) as the standard reference control used. The MolDock scores (ranging between -189.67 and -142.47 kcal/mol) of these newly designed compounds in the NA binding cavity were also better than the hit template 21 with a MolDock score of -125.33 kcal/mol and zanamivir standard drug (-136.36 kcal/mol). In addition, the conformational stability of the best-designed compound 21a in the NA binding cavity was further studied through the MD simulation of 100 ns. Moreover, the drug-likeness and ADMET predictions of these designed compounds showed their good oral bioavailability and pharmacokinetic profiling respectively. More so, the DFT calculations also revealed the relevance of these designed compounds in view of their smaller band energy gaps from the frontier molecular orbital calculations. This study could serve as a reliable in-silico perspective for the search and discovery of potential anti-influenza agents.
The increasing quest for therapeutic alternatives in treating non-communicable chronic diseases like obesity has propelled research into bioactive peptides, with a particular focus on milk due to its rich protein composition and associated health benefits. Milk fermentation, a traditional process in dairy production, enhances the bioactivity of peptides, broadening their potential therapeutic uses. This study investigated the anti-obesity potential of peptides from bovine milk fermented by Lacticaseibacillus casei LBC 237, identifying 143 peptides, notably LGPV and EVPMP. In silico analyses revealed that LGPV and EVPMP biopeptides exhibited significant interactions with target proteins, employing various molecular interactions such as Van der Waals forces, hydrogen bonds, and electrostatic interactions. These peptides shared common binding sites in some enzymes, suggesting a similar mode of interaction between molecule and target protein, akin to key pharmaceuticals recommended for treating these pathologies. Furthermore, amino acid characteristics present in the peptides, including hydrophobic residues like Leucine, Glutamate, Valine, and Proline, proved essential for their bioactive and inhibitory activities. These findings highlight the potential of LGPV and EVPMP biopeptides as therapeutic agents in managing obesity and metabolic disorders. They provide important insights into their mechanisms of action, paving the way for future research to apply them practically in preventing and treating metabolic conditions.
The activity of Seborrheic dermatitis on the skin of children still remains of the dermatoses of male and female babies in the early days of their existence. Acalypha wilkesiana L have been employed by mothers to combat Seborrheic dermatitis, yet, the descriptors responsible for such activity as well as the nonbonding interactions between the selected phytochemicals and stearoyl-CoA desaturase has not been explored. The studied compounds were optimized using Spartan’14 software as well as molecular operating environments (MOE) for docking, Cytoscape software for compound-protein interaction network, Gromacs for molecular dynamic simulation as well ADMETSar for pharmacokinetics studies. The selected compounds proved to have anti-stearoyl-CoA desaturase properties via the calculated descriptors obtained from the chemical compounds obtained from Acalypha wilkesiana L as well as from the result from molecular modeling studies. The Pharmacokinetics results were observed and reported appropriately.
The murrcidae gastropod operculum has many therapeutic uses in ayurveda, including treating cancer, gastric, hepatic, cardiovascular, and immunological disorders. Antibacterial, cell reinforcement, FTIR, and mass spectrum datas were used to identify important functional groups and chemical constituents in Chicoreus ramosus operculum concentrate. At 100 mg/L, the operculum extract showed stronger inhibitory movement (125 mm) against Bacillus subtilis and less (08 mm) against Staphylococcus aureus. Operculum extract’s biochemical composition, total antioxidant properties, protein denaturation, metal chelation movement, all-out cell reinforcement action, and anti-diabetic action were 85.71%, 80.98%, 32.03%, and 76.47% at 1000 µg/mL concentration. The operculum remove FTIR showed nine significant groups, including amines, esters, and fragrant mixtures. 11 dynamic mixtures from GC–MS analysis of operculum rough concentrate. These bioactive fractions interacted with IL 23 in molecular docking experiments. Androst-1-en-3-one, Bis (2-ethylhexyl) phthalate, and 3-Methoxy-2,4,5-trifluorobenzoic acid had the highest docking scores and target protein receptor interactions. -11.9 kcal/mol, -08.6 kcal/mol and -7.7 kcal/mol are the maximum scores. These compounds are therapeutic and antimicrobial. These bioactive compounds in operculum extracts allow C. ramosus to be used in conventional medicine and may lead to the development of new drugs.
A variety of medicinal compounds, including 4,6-di(1H-indol-3-yl)-1,6-dihydropyrimidin-2-amine, were synthesized through a single-step, multicomponent, stepwise reaction. In this reaction, a mixture of 1H-indole-3-Carbaldehyde, 1-(1H-indol-3-yl) ethanone and guanidine nitrate in ethanol was refluxed. The synthesized compounds were characterized using 1H NMR and 13C NMR studies and their antimicrobial activities against Escherichia coli, Staphylococcus aureus, Aspergillus niger and Aspergillus flavus were evaluated. Molecular docking analysis revealed specific amino acid residues (LEU704, GLY708, LEU707, GLN711, MET749, PHE764, VAL746, MET787, MET745, LEU873, HIS874, VA; 903, MET742, ILE898, MET895, ILE899, TRP741, THR877, P HE 876, LEU701, MET780) are involved in the interaction between androgen receptor and ligand. The optimal interaction and docking score were observed (7.0 kcal/mol).
Breast cancer remains a significant global health concern, necessitating the exploration of novel preventive and therapeutic strategies. Dietary interventions have gained substantial attention due to their potential to modulate cancer risk and progression. Millets, a group of small-seeded grasses, have emerged as promising candidates in this regard, owing to their rich nutritional composition and diverse bioactive compounds. Among these bioactive compounds, phytate antinutrients have garnered considerable interest for their potential health benefits. This review aims to unravel the intricacies of phytate antinutrients in millets and their therapeutic implications in breast cancer. Phytates are naturally occurring compounds present in various plant-based foods, including millets, and are known for their ability to chelate minerals and inhibit their bioavailability. However, recent research has shed light on the multifaceted properties of phytates, highlighting their potential as functional bioactive molecules. Phytates exhibit various anticancer properties, including “antioxidant, anti-inflammatory, and anti-proliferative effects”, which have been shown to inhibit the growth and progression of breast cancer cells. Additionally, phytates have been reported to modulate key signaling pathways involved in cancer development, such as PI3K/Akt, MAPK, and NF-κB, thereby exerting their anticancer effects. Moreover, phytates demonstrate the potential to enhance the efficacy of conventional breast cancer treatments, such as chemotherapy and radiation therapy, while mitigating their adverse effects. Furthermore, the bioavailability and metabolism of phytates are complex processes influenced by factors such as food processing, gut microbiota composition, and genetic variations. Understanding these intricacies is crucial for harnessing the full potential of phytates in breast cancer prevention and treatment. In conclusion, this review provides a comprehensive overview of the intricate roles of phytate antinutrients in millets and their therapeutic implications in breast cancer. The findings suggest that millets, as a rich source of phytates, could be incorporated into dietary strategies to reduce breast cancer risk and complement existing therapeutic approaches. However, further research is warranted to elucidate the precise mechanisms of action, optimal dosage, and potential synergistic effects with other bioactive compounds. The information that is given here is supported by accurate facts and arguments that have undergone rigorous scrutiny.
A number of dengue viruses can seriously impact public health, and their spread has long been a concern. The development and administration of antiviral drugs have played a crucial role in combating viral infections in recent years. These drugs have shown that they can effectively inhibit viral replication and alleviate associated viral complications. The aim of this article is to provide an overview of current evidence on the effectiveness of administered antiviral drugs in controlling viral replication and treating viral problems. In the present study, the PyRx tool was used to docked proteins and ligands. In summary, the present study shows that rosmarinic acid has remarkable docking values against various dengue viral targets. Specifically, it shows a docking value of -8.0 for DENV1-E111, -8.1 for the RNA-dependent RNA polymerase (NS5), -8.2 for the non-structural A chain protein 1 (NS1), and -8.6 for the RNA helicase. These results suggest that rosmarinic acid may have an antiviral effect against the virus's target proteins. Further research is needed to investigate the therapeutic effects of rosmarinic acid in fighting viral infections. In addition, many enzymatic activities of rosmarinic acid have been reported by the PASS (Prediction of Activity Spectra for Substances) tool. The present investigation led to the definitive conclusion that rosmarinic acid possesses remarkable antiviral properties. The present study is promising for future applications, particularly in the search for a drug molecule that can effectively combat a variety of viral infections.
Alzheimer’s disease (AD) is a brain disorder that is known to be one of the deadliest diseases affecting humanity, especially adults from the age of sixty (60) years and above. It mostly affects thinking ability, behaviour and social skills, eventually, AD causes the brain to shrink and brain cells to die. To curb the menace of this disease, virtual screening of potent, non-toxic hybrid natural therapeutic inhibitors was performed on some inhibitors of AD. We performed simulations on the screened compounds and predicted their druggability. A model with satisfactory statistical properties was developed in this study. The ligands underwent molecular docking, C-19 exhibited the highest docked score of -12.8 kcal/mol against the target, while the referenced compound (harmine) indicated the lowest docked score of -8.2 kcal/mol. The docked complex was validated using molecular dynamic simulations. Trajectory plots of C-19 were obtained and found to be stable. C-19 was stable during the 100 ns intervals which implies that the compounds were better than the referenced compound. In addition, ADMET has demonstrated that these ligands have good pharmacokinetic properties. All the evaluations were more comprehensive and beneficial to researchers and the medical community as outstanding results were obtained.
Cowhide collagen hydrolysates (CCHs) are peptides and amino acids obtained from the partial hydrolysis of collagen. These have numerous potential applications in the food, biomedical, and pharmaceutical industries. The study analyzed the physicochemical, antioxidant, and anti-atherosclerosis properties of collagen hydrolysates (CCHs) from cowhide using in silico methods. Proteins were identified in silico based on their molecular weights and origin from the protein database (UniProtKB). Using bioinformatics tools, numerous physicochemical properties (toxicity and amino acid composition) were determined. The identified proteins were subsequently subjected to an in silico enzymatic hydrolysis using pepsin, thermolysin, and proteinase K. The peptides obtained were characterized. Molecular docking was conducted between the peptides generated in silico and the three target enzymes (3-Hydroxy-3-Methylglutaryl-CoA (HMG-CoA) reductase, cyclooxygenase-2, and Nicotinamide Adenine Dinucleotide Phosphate (NADPH) oxidase). Two cowhide collagens were identified, F1MJQ6 and G3MZI7, with molecular weights of 172,076 and 184,867 Da, respectively. A compositional analysis of F1MJQ6 and G3MZI7 revealed the significant presence of glycine residues at 25% and 23%, and proline residues at 16% and 18%, respectively. The G3MZI7 and F1MJQ6 proteins exhibited a high concentration of both essential and semiessential amino acids. The molecular docking results indicate that the antioxidant peptides ADF, PHF, and LW (novel potential anti-atherosclerosis peptides released by enzymatic hydrolysis with pepsin, thermolysin, and proteinase K) are the most promising candidates for further development as inhibitors of HMG-CoA reductase, cyclo-oxygenase-2, and NADPH oxidase. In silico analysis revealed that cowhide collagen hydrolysates exhibited particularly significant antioxidant and anti-atherosclerosis properties.