Search Results (29)

Background: Formulating poorly water-soluble drugs poses significant challenges due to their limited solubility and bioavailability. Loratadine (LTD), classified as a BCS II molecule, exhibits notably low solubility, leading to reduced bioavailability. Objective: This study aims to enhance the dissolution rate of LTD through the utilization of the wet granulation process using Tocopheryl polyethylene glycol 1000 succinate (TPGS). Methods: A Design-of-Experiment methodology was adopted to investigate and optimize the formulation variables for preparing an oral delivery system of LTD with improved dissolution properties. The levels of TPGS (2–6% w/w), as a surfactant, and sodium starch glycolate (SSG; 2–8% w/w), as a super-disintegrant, were established as independent variables in the formulations. Loratadine was granulated in the presence of TPGS, and the resultant granules were subsequently compressed into tablets. The granules and tablets produced were then subjected to characterization. Results: ANOVA analysis indicated that both TPGS and SSG had a significant (p < 0.05) influence on the critical characteristics of the obtained granules and tablets, with TPGS showing a particularly notable effect. The optimal concentrations of TPGS and SSG for the development of LTD tablets with the necessary quality attributes were identified as 5.0% w/w and 2.0% w/w, respectively, through optimization utilizing the desirability function. The tablets produced at these optimized concentrations displayed favorable properties concerning their mechanical strength (5.72 ± 0.32 KP), disintegration time (7.11 ± 1.08 min.), and release profile (86.21 ± 1.61%). Conclusions: In conclusion, incorporating TPGS in the granulation process shows promise in improving the dissolution profile of poorly water-soluble drugs and demonstrated formulation robustness. Full article

Loratadine (LOR) is a second-generation antihistamine that exhibits a low and variable oral bioavailability (10–40%) and delayed onset owing to poor solubility and an extensive first-pass effect. Therefore, in light of the clinical need, the main goal of the present study was to develop sublingual fast-dissolving thin films of LOR–citric acid co-amorphous systems (LOR-CAs) with the aim of eliciting a faster onset and improving the bioavailability. We formulated sublingual fast-dissolving thin films of LOR by a film-casting technique using hydrophilic polymers like hydroxypropyl methylcellulose (HPMC E15), polyvinyl pyrrolidone K30 (PVP K30), and hydroxypropyl cellulose EL (HPC-EF) and citric acid as a pH modulator, while glycerin served as a plasticizer. The sublingual fast-dissolving thin films were characterized by FTIR, SEM, DSC, and XRD and evaluated for in vitro dissolution and ex vivo mucoadhesion. The best formulation (F1) developed using HPMC E15 as a polymer, glycerin as a plasticizer, and citric acid as a pH modulator was found to be the optimized formulation as it was smooth, clear, flexible, and displayed good mucoadhesion (11.27 ± 0.418 gm/cm²) and uniform thickness (0.25 ± 0.02 mm). The formulation F1 was found to display a significantly shorter DT (30.30 ± 0.6 s) and rapid release of LOR (92.10 ± 2.3% in 60 min) compared to other formulations (ANOVA, p < 0.001). The results indicated that the prepared sublingual films are likely to elicit a faster therapeutic effect, avoid first-pass metabolism, and improve the bioavailability. Full article

Neurological injury is a crucial problem that interferes with the therapeutic use of vinca alkaloids as well as the quality of patient life. This study was conducted to assess the impact of using loratadine or diosmin/hesperidin on neuropathy induced by vinca alkaloids. Patients were randomized into one of three groups as follows: group 1 was the control group, group 2 received 450 mg diosmin and 50 mg hesperidin combination orally twice daily, and group 3 received loratadine 10 mg orally once daily. Subjective scores (numeric pain rating scale, douleur neuropathique 4, and functional assessment of cancer therapy/gynecologic oncology group–neurotoxicity (FACT/GOG-Ntx) scores), neuroinflammation biomarkers, adverse drug effects, quality of life, and response to chemotherapy were compared among the three groups. Both diosmin/hesperidin and loratadine improved the results of the neurotoxicity subscale in the FACT/GOG-Ntx score (p < 0.001, p < 0.01 respectively) and ameliorated the upsurge in neuroinflammation serum biomarkers. They also reduced the incidence and timing of paresthesia (p = 0.001 and p < 0.001, respectively) and dysuria occurrence (p = 0.042). Both loratadine and diosmin/hesperidin attenuated the intensity of acute neuropathy triggered by vinca alkaloids. Furthermore, they did not increase the frequency of adverse effects or interfere with the treatment response. Full article

Loratadine (LRD), a non-sedating and slow-acting antihistamine, is often given in combination with short-onset chlorpheniramine maleate (CPM) to increase efficacy. However, LRD has poor water solubility resulting in low bioavailability. The aim of this study was to improve LRD solubility by preparing co-amorphous LRD-CPM. However, the obtained co-amorphous LRD-CPM recrystallized rapidly, and the solubility of LRD returned to a poor state again. Therefore, co-amorphous LRD-CPM solid dispersions using polyvinylpyrrolidone (PVP) as a carrier were prepared. The obtained solid dispersions were characterized using X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FT-IR). The solubility, dissolution, and mechanism of drug release from the LRD-CPM/PVP co-amorphous solid dispersions were studied and compared with those of intact LRD, LRD/PVP solid dispersions, and co-amorphous LRD-CPM mixtures. The results from XRPD and DSC confirmed the amorphous form of LRD in the co-amorphous solid dispersions. The FTIR results indicated that there was no intermolecular interaction between LRD, CPM, and PVP. In conclusion, the obtained LRD-CPM/PVP co-amorphous solid dispersions can successfully increase the water solubility and dissolution of LRD and extend the amorphous state of LRD without recrystallization. Full article

The purpose of the study is to develop and assess mucoadhesive in situ nasal gel formulations of loratadine and chlorpheniramine maleate to advance the bioavailability of the drug as compared to its conventional dosage forms. The influence of various permeation enhancers, such as EDTA (0.2% w/v), sodium taurocholate (0.5% w/v), oleic acid (5% w/v), and Pluronic F 127 (10% w/v), on the nasal absorption of loratadine and chlorpheniramine from in situ nasal gels containing different polymeric combinations, such as hydroxypropyl methylcellulose, Carbopol 934, sodium carboxymethylcellulose, and chitosan, is studied. Among these permeation enhancers, sodium taurocholate, Pluronic F127 and oleic acid produced a noticeable increase in the loratadine in situ nasal gel flux compared with in situ nasal gels without permeation enhancer. However, EDTA increased the flux slightly, and in most cases, the increase was insignificant. However, in the case of chlorpheniramine maleate in situ nasal gels, the permeation enhancer oleic acid only showed a noticeable increase in flux. Sodium taurocholate and oleic acid seems to be a better and efficient enhancer, enhancing the flux > 5-fold compared with in situ nasal gels without permeation enhancer in loratadine in situ nasal gels. Pluronic F127 also showed a better permeation, increasing the effect by >2-fold in loratadine in situ nasal gels. In chlorpheniramine maleate in situ nasal gels with EDTA, sodium taurocholate and Pluronic F127 were equally effective, enhancing chlorpheniramine maleate permeation. Oleic acid has a better effect as permeation enhancer in chlorpheniramine maleate in situ nasal gels and showed a maximum permeation enhancement of >2-fold. Full article

Spray drying is one of the most frequently used solvent-based processes for manufacturing amorphous solid dispersions (ASDs). However, the resulting fine powders usually require further downstream processing when intended for solid oral dosage forms. In this study, we compare properties and performance of spray-dried ASDs with ASDs coated onto neutral starter pellets in mini-scale. We successfully prepared binary ASDs with a drug load of 20% Ketoconazole (KCZ) or Loratadine (LRD) as weakly basic model drugs and hydroxypropyl-methyl-cellulose acetate succinate or methacrylic acid ethacrylate copolymer as pH-dependent soluble polymers. All KCZ/ and LRD/polymer mixtures formed single-phased ASDs, as indicated by differential scanning calorimetry, X-ray powder diffraction and infrared spectroscopy. All ASDs showed physical stability for 6 months at 25 °C/65% rH and 40 °C/0% rH. Normalized to their initial surface area available to the dissolution medium, all ASDs showed a linear relationship of surface area and solubility enhancement, both in terms of supersaturation of solubility and initial dissolution rate, regardless of the manufacturing process. With similar performance and stability, processing of ASD pellets showed the advantages of a superior yield (>98%), ready to use for subsequent processing into multiple unit pellet systems. Therefore, ASD-layered pellets are an attractive alternative in ASD-formulation, especially in early formulation development at limited availability of drug substance. Full article

This study aimed at the preparation and characterization of co-amorphous loratadine–citric acid orally disintegrating dosage forms (ODx). A co-amorphous loratadine–citric acid was prepared by solvent evaporation method in three different molecular ratios. DSC, FTIR, and dissolution studies have been conducted for the binary system. The co-amorphous system was used to obtain oral lyophilizates and orally disintegrating tablets by direct compression. Diameter, thickness, hardness, disintegration time, uniformity of mass, and dissolution was determined for the dosage forms. DSC curves showed a lack of sharp endothermic peaks for the binary systems. FTIR spectra presented a hypsochromic modification of the characteristic peaks. Dissolution studies indicated a five-fold increase in the dissolved amount compared to pure loratadine in water. Disintegration times of direct compression ODx varied in the range of 34–41 s and for freeze-dried ODx in the range of 8–9 s. Friability was under 1% in all cases. The dissolution of loratadine in buffer solution at pH = 1 was almost complete. In conclusion binary systems of loratadine and citric acid enhance solubility and combined with the orally disintegrating pharmaceutical form also increase patient compliance. Full article

SARS-CoV-2 infections are highly correlated with the overexpression of pro-inflammatory cytokines in what is known as a cytokine storm, leading to high fatality rates. Such infections are accompanied by SIRS, ARDS, and sepsis, suggesting a potential link between the three phenotypes. Currently, little is known about the transcriptional similarity between these conditions. Herein, weighted gene co-expression network analysis (WGCNA) clustering was applied to RNA-seq datasets (GSE147902, GSE66890, GSE74224, GSE177477) to identify modules of highly co-expressed and correlated genes, cross referenced with dataset GSE160163, across the samples. To assess the transcriptome similarities between the conditions, module preservation analysis was performed and functional enrichment was analyzed in DAVID webserver. The hub genes of significantly preserved modules were identified, classified into upregulated or downregulated, and used to screen candidate drugs using Connectivity Map (CMap) to identify repurposed drugs. Results show that several immune pathways (chemokine signaling, NOD-like signaling, and Th1 and Th2 cell differentiation) are conserved across the four diseases. Hub genes screened using intramodular connectivity show significant relevance with the pathogenesis of cytokine storms. Transcriptomic-driven drug repurposing identified seven candidate drugs (SB-202190, eicosatetraenoic-acid, loratadine, TPCA-1, pinocembrin, mepacrine, and CAY-10470) that targeted several immune-related processes. These identified drugs warrant further study into their efficacy for treating cytokine storms, and in vitro and in vivo experiments are recommended to confirm the findings of this study. Full article

A multicomponent pharmaceutical that contains loratadine, paracetamol, and pseudoephedrine was quantified using HPLC-PDA. The three analytes were well-separated and quantified in the dosage form on a C-18 column using a gradient mobile phase. A quality by design strategy was followed to achieve the challenging separation. Screening and optimization steps were carried out to investigate the effect of many factors on the studied responses with a minimum number of runs. The ANOVA of the factorial model showed that % acetonitrile (factor A), flow rate (factor B), and pH (factor C) were significant. The detection of the analytes’ peaks was carried out using a PDA detector at 248nm for loratadine and paracetamol, and 214 nm for pseudoephedrine. The second method was SPE-HPLC-MS, where the three analytes and desloratadine, the active metabolite of loratadine, were quantified in spiked plasma and urine, using betamethasone valerate as an internal standard. The recovery of the analytes from body fluids was above 96%, and the LOQ was below 0.5 ng/mL. The validation of the developed HPLC-PDA method was achieved as per ICH guidelines, whereas the HPLC-MS method was validated according to FDA guidelines for bioanalytical method validation. The results were compared with the reported method, and no significant differences were found. Full article

The development of suitable formulations for the pediatric population remains a challenging field with great advances reported every year in terms of excipients and technology. When developing pediatric formulations, the acceptability of medicines represents a key element to consider. For this reason, milk can be a widely accepted excipient with taste-masking properties and supplementary advantages for drug solubility. In recent years, the orodispersible dosage forms have come onto the market as child-friendly formulations. The current study aimed to develop freeze-dried orodispersible dosage forms containing bovine milk or infant formulae as the main component. In the first stage, an exploratory study evaluated the mechanical properties of placebo milk formulations and the suitability of milk as a matrix-forming agent. As the appropriate mechanical strength to withstand manipulation was demonstrated, milk oral lyophilizates were loaded with a poorly soluble model API, loratadine. Hence, a D-optimal design was conducted to prepare milk lyophilizates with loratadine and to evaluate the effects of three factors (dose of loratadine, the lyophilizate size, and the type of milk) and their interactions. Finally, three formulations were prepared to confront the predictions of the DoE and further studied to thoroughly understand the observed effects. The experimental results showed the potential of milk in the development of oral lyophilizates loaded with different doses of suspended API. Full article

Antihistamines have potent efficacy to alleviate COVID-19 (Coronavirus disease 2019) symptoms such as anti-inflammation and as a pain reliever. However, the pharmacological mechanism(s), key target(s), and drug(s) are not documented well against COVID-19. Thus, we investigated to decipher the most significant components and how its research methodology was utilized by network pharmacology. The list of 32 common antihistamines on the market were retrieved via drug browsing databases. The targets associated with the selected antihistamines and the targets that responded to COVID-19 infection were identified by the Similarity Ensemble Approach (SEA), SwissTargetPrediction (STP), and PubChem, respectively. We described bubble charts, the Pathways-Targets-Antihistamines (PTA) network, and the protein–protein interaction (PPI) network on the RPackage via STRING database. Furthermore, we utilized the AutoDock Tools software to perform molecular docking tests (MDT) on the key targets and drugs to evaluate the network pharmacological perspective. The final 15 targets were identified as core targets, indicating that Neuroactive ligand–receptor interaction might be the hub-signaling pathway of antihistamines on COVID-19 via bubble chart. The PTA network was constructed by the RPackage, which identified 7 pathways, 11 targets, and 30 drugs. In addition, GRIN2B, a key target, was identified via topological analysis of the PPI network. Finally, we observed that the GRIN2B-Loratidine complex was the most stable docking score with −7.3 kcal/mol through molecular docking test. Our results showed that Loratadine might exert as an antagonist on GRIN2B via the neuroactive ligand–receptor interaction pathway. To sum up, we elucidated the most potential antihistamine, a key target, and a key pharmacological pathway as alleviating components against COVID-19, supporting scientific evidence for further research. Full article

Loratadine is an anti-histamine routinely used for treating allergies. However, recent findings have shown that Loratadine may also have anti-inflammatory functions, while their exact mechanisms have not yet been fully uncovered. In this paper, we investigated whether Loratadine can be utilized as an anti-inflammatory drug through a series of in vitro and in vivo experiments using a murine macrophage cell line and an acute gastritis mouse model. Loratadine was found to dramatically reduce the expression of pro-inflammatory genes, including MMP1, MMP3, and MMP9, and inhibit AP-1 transcriptional activation, as demonstrated by the luciferase assay. Therefore, we decided to further explore its role in the AP-1 signaling pathway. The expression of c-Jun and c-Fos, AP-1 subunits, was repressed by Loratadine and, correspondingly, the expression of p-JNK, p-MKK7, and p-TAK1 was also inhibited. In addition, Loratadine was able to reduce gastric bleeding in acute gastritis-induced mice; Western blotting using the stomach samples showed reduced p-c-Fos protein levels. Loratadine was shown to effectively suppress inflammation by specifically targeting TAK1 and suppressing consequent AP-1 signaling pathway activation and inflammatory cytokine production. Full article

Data from several cohorts of coronavirus disease 2019 (COVID-19) suggest that the most common comorbidities for severe COVID-19 disease are the elderly, high blood pressure, and diabetes; however, it is not currently known whether the previous use of certain drugs help or hinder recovery. This study aims to explore the association of previous hospitalisation use of medication on the mortality of COVID-19 disease. A retrospective case-control from two hospitals in Madrid, Spain, included all patients aged 18 years or above hospitalised with a diagnosis of COVID-19. A Propensity Score matching (PSM) analysis was performed. Confounding variables were considered to be age, sex, and the number of comorbidities. Finally, 3712 patients were included. Of these, 687 (18.5%) patients died (cases). The 22,446 medicine trademarks used previous to admission were classified according to the ATC, obtaining 689 final drugs; all of them were included in PSM analysis. Eleven drugs displayed a reduction in mortality: azithromycin, bemiparine, budesonide-formoterol fumarate, cefuroxime, colchicine, enoxaparin, ipratropium bromide, loratadine, mepyramine theophylline acetate, oral rehydration salts, and salbutamol sulphate. Eight final drugs displayed an increase in mortality: acetylsalicylic acid, digoxin, folic acid, mirtazapine, linagliptin, enalapril, atorvastatin, and allopurinol. Medication associated with survival (anticoagulants, antihistamines, azithromycin, bronchodilators, cefuroxime, colchicine, and inhaled corticosteroids) may be candidates for future clinical trials. Drugs associated with mortality show an interaction with the underlying conditions. Full article

A systematic chemical investigation of the deep-sea-derived fungus Penicillium solitum MCCC 3A00215 resulted in the isolation of one novel polyketide (1), two new alkaloids (2 and 3), and 22 known (4–25) compounds. The structures of the new compounds were established mainly on the basis of exhaustive analysis of 1D and 2D NMR data. Viridicatol (13) displayed moderate anti-tumor activities against PANC-1, Hela, and A549 cells with IC₅₀ values of around 20 μM. Moreover, 13 displayed potent in vitro anti-food allergic activity with an IC₅₀ value of 13 μM, compared to that of 92 μM for the positive control, loratadine, while indole-3-acetic acid methyl ester (9) and penicopeptide A (10) showed moderate effects (IC₅₀ = 50 and 58 μM, respectively). Full article

Background: Pharmacological targeting aberrant activation of epidermal growth factor receptor tyrosine kinase signaling is an established approach to treating lung adenocarcinoma. Osimertinib is a tyrosine kinase approved and effective in treating lung adenocarcinomas that have one of several common activating mutations in epidermal growth factor receptor. The emergence of resistance to osimertinib after a year or two is the rule. We developed a five-drug adjuvant regimen designed to increase osimertinib’s growth inhibition and thereby delay the development of resistance. Areas of Uncertainty: Although the assembled preclinical data is strong, preclinical data and the following clinical trial results can be discrepant. The safety of OPALS drugs when used individually is excellent. We have no data from humans on their tolerability when used as an ensemble. That there is no data from the individual drugs to suspect problematic interaction does not exclude the possibility. Data Sources: All relevant PubMed.org articles on the OPALS drugs and corresponding pathophysiology of lung adenocarcinoma and glioblastoma were reviewed. Therapeutic Opinion: The five drugs of OPALS are in wide use in general medicine for non-oncology indications. OPALS uses the anti-protozoal drug pyrimethamine, the antihistamine cyproheptadine, the antibiotic azithromycin, the antihistamine loratadine, and the potassium sparing diuretic spironolactone. We show how these inexpensive and generically available drugs intersect with and inhibit lung adenocarcinoma growth drive. We also review data showing that both OPALS adjuvant drugs and osimertinib have data showing they may be active in suppressing glioblastoma growth. Full article