Antihistamines Research Articles

Physiochemical investigation of the excipients mixed micelles for improvement of encapsulation and controlled release of antihistamine drugs

Today's biotechnology and pharmaceutical industries significantly depend on amphiphilic excipients due to their enhanced drug-binding characteristics for delivery systems. This study emphasizes the significance of pharmaceutical excipients that could produce mixed micelles to enhance drug delivery systems. Tartrazine (TAZ) and cetyltrimethylammonium bromide (CTAB) mixed micellization were stabilized using surface tension, conductivity, and steady-state fluorescence quenching techniques. Using the Levenberg-Maquardt least squares technique, the CMC values derived from the conductivity experimental data were also taken into account. Clint's, Rubingh's, and Motumura's approaches were used to investigate the characteristics of mixed micelles to comprehend the effectiveness of TAZ-CTAB mixtures. The TAZ-CTAB-mixed micelles were shown to have a more potent synergistic interaction. The binding constant (LogKb), mean ion occupancy (i0), and encapsulation efficiency (% EE) of the antihistamines cetirizine hydrochloride (CTZ) and chlorpheniramine maleate (CPM) was enhanced by raising the TAZ from αTAZ 0.1 to 0.9999. In addition, the controlled release of CTZ and CPM in PBS at pH 7.4 was around 50 % in mixed micelles after 50 h at αTAZ 0.7 to 0.9. In summary, the dyes and surfactants might be utilized in a mole fraction ratio to improve the binding properties of active medicinal ingredients while concurrently lowering the quantity of excipients needed in pharmaceutical formulations.

Repurposing of the antihistamine mebhydrolin napadisylate for treatment of Zika virus infection

Zika virus (ZIKV) infection can lead to severe neurological disorders and fetal defects, which has become a public health problem worldwide. However, effective clinical treatment for ZIKV infection was still arduous. Antihistamines are attractive candidates for drug repurposing due to their low price and widespread availability. Here we screened FDA-approved antihistamine drugs to obtain anti-ZIKV candidate compounds and identified mebhydrolin napadisylate (MHL) that exhibits the potent inhibition of ZIKV infection in various cell lines in a histamine H1 receptor-independent manner. Mechanistic studies suggest that MHL acts as a ZIKV NS5 RNA-dependent RNA polymerase (RdRp) inhibitor, supported by a structure–activity relationship (SAR) analysis showing the correlation between the inhibitory effect upon viral RNA synthesis and ZIKV infectivity. Furthermore, MHL was shown to bind ZIKV NS5 RdRp in vitro and predicted to interact with key residues at the active site of ZIKV NS5 RdRp by molecular docking analysis. Our data together suggest that MHL suppresses ZIKV infection through the inhibition of ZIKV NS5 RdRp activity. This study highlights that MHL might be a promising clinical anti-ZIKV therapeutic.

Systemic and Ocular Anti-Inflammatory Mechanisms of Green Tea Extract on Endotoxin-Induced Ocular Inflammation.

IntroductionGreen tea extract (GTE) alleviated ocular inflammations in endotoxin-induced uveitis (EIU) rat model induced by lipopolysaccharide (LPS) but the underlying mechanism is unclear.ObjectivesTo investigate the systematic and local mechanisms of the alleviation by untargeted metabolomics using liquid chromatography-tandem mass spectrometryMethodsSprague-Dawley rats were divided into control group, LPS treatment group, and LPS treatment group treated with GTE two hours after LPS injection. The eyes were monitored by slip lamp and electroretinography examination after 24 hours. The plasma and retina were collected for metabolomics analysisResultsIn LPS treated rats, the iris showed hyperemia. Plasma prostaglandins, arachidonic acids, corticosteroid metabolites, and bile acid metabolites increased. In the retina, histamine antagonists, corticosteroids, membrane phospholipids, free antioxidants, and sugars also increased but fatty acid metabolites, N-acetylglucosamine-6-sulphate, pyrocatechol, and adipic acid decreased. After GTE treatment, the a- and b- waves of electroretinography increased by 13%. Plasma phosphorylcholine lipids increased but plasma prostaglandin E1, cholanic metabolites, and glutarylglycine decreased. In the retina, tetranor-PGAM, pantothenic derivatives, 2-ethylacylcarinitine, and kynuramine levels decreased but anti-oxidative seleno-peptide level increased. Only phospholipids, fatty acids, and arachidonic acid metabolites in plasma and in the retina had significant correlation (p < 0.05, r > 0.4 or r < -0.4).ConclusionsThe results showed GTE indirectly induced systemic phosphorylcholine lipids to suppress inflammatory responses, hepatic damage, and respiratory mitochondrial stress in EIU rats induced by LPS. Phospholipids may be a therapeutic target of GTE for anterior chamber inflammation

Formulation of Levocetirizine-Loaded Core-Shell Type Nanofibrous Orally Dissolving Webs as a Potential Alternative for Immediate Release Dosage Forms.

Several applications of nanofiber-based systems are based on their corresponding functionality-related properties, which often cannot be satisfied by a fiber web with a monolithic structure because of the various physicochemical properties and amounts of embedded compounds. Therefore, one of the main directions in the development of fiber systems is creating core–shell type complex fiber structures that can provide application-specific properties to the fiber matrix. The present study aimed to formulate levocetirizine-loaded core–shell type hydrophilic polymer-based fibrous systems. The core phase contained the antihistamine levocetirizine, while the permeation enhancer (Na-taurocholate), the local pH regulator (citric acid), and the cyclodextrin used as a taste masking agent were included in the shell phase of the fibrous formulation. Scanning electron microscopy images indicated that a randomly oriented homogeneous fibrous structure was obtained, while the Raman mapping and chemometric analysis confirmed the partially formed core–shell structure. A fast release rate of the antihistamine drug from the complex structural fibrous system was obtained (within 1 min complete dissolution can be observed) due to its increased surface area to volume ratio and its more favorable wettability properties, which consequently allows for more erosion. The masking properties against the unpleasant bitter taste of API of the formulated complex nanostructure were confirmed by the results of the electronic tongue. The formulated complex nanostructure enabled fast and complete release of the API, providing a potential enhancement in the rate and extent of absorption while masking the unpleasant taste of levocetirizine, which has a high impact on the patient adherence. All in all, the results show that the developed orally dissolving fibrous web formulation can be a potential alternative to the commercially available orally disintegrating tablets.

Papules, pustules, and rhinoconjunctivitis in a 4-year-old

Papules, pustules, and rhinoconjunctivitis in a 4-year-old

The Anti-Histamine Azelastine, Identified by Computational Drug Repurposing, Inhibits Infection by Major Variants of SARS-CoV-2 in Cell Cultures and Reconstituted Human Nasal Tissue.

Background and purpose: The COVID-19 pandemic continues to pose challenges, especially with the emergence of new SARS-CoV-2 variants that are associated with higher infectivity and/or compromised protection afforded by the current vaccines. There is a high demand for additional preventive and therapeutic strategies effective against this changing virus. Repurposing of approved or clinically tested drugs can provide an immediate solution. Experimental Approach: We applied a novel computational approach to search among approved and commercially available drugs. Antiviral activity of a predicted drug, azelastine, was tested in vitro in SARS-CoV-2 infection assays with Vero E6 cells, Vero cells stably overexpressing the human TMPRSS2 and ACE2 proteins as well as on reconstituted human nasal tissue using the predominant variant circulating in Europe in summer 2020, B.1.177 (D614G variant), and its emerging variants of concern; B.1.1.7 (alpha), B.1.351 (beta) and B.1.617.2 (delta) variants. The effect of azelastine on viral replication was assessed by quantification of viral genomes by droplet digital PCR or qPCR. Key results: The computational approach identified major drug families, such as anti-infective, anti-inflammatory, anti-hypertensive, antihistamine, and neuroactive drugs. Based on its attractive safety profile and availability in nasal formulation, azelastine, a histamine 1 receptor-blocker was selected for experimental testing. Azelastine reduced the virus-induced cytopathic effect and SARS-CoV-2 copy numbers both in preventive and treatment settings upon infection of Vero cells with an EC50 of 2.2–6.5 µM. Comparable potency was observed with the alpha, beta and delta variants. Furthermore, five-fold dilution (containing 0.02% azelastine) of the commercially available nasal spray formulation was highly potent in inhibiting viral propagation in reconstituted human nasal tissue. Conclusion and Implications: Azelastine, an antihistamine available as nasal sprays developed against allergic rhinitis may be considered as a topical prevention or treatment of nasal colonization by SARS-CoV-2. A Phase 2 efficacy indicator study with azelastine-containing nasal spray that was designed based on the findings reported here has been concluded recently, confirming accelerated viral clearance in SARS-CoV-2 positive subjects.

Effectiveness of bilastine and fexofenadine among allergic Rhinitis patients in Ranchi, Jharkhand, India.

Allergic rhinitis is a worldwide health problem which impairs quality of life and interferes with daily activities. Untreated allergic rhinitis also carries a significant financial burden for the society. Bilastine, a novel second-generation antihistaminic drug that is highly selective for the H1 histamine receptor, has a rapid onset and prolonged duration of action. Thus, the aim of our study was to compare the effectiveness of bilastine and fexofenadine in treatment of allergic Rhinitis patients. 104 patients were enrolled who have fulfilled the inclusion criteria for the study from the OPD of Ear, Nose and Throat Department. Patients were divided randomly in two groups A and B. Patients of group A were allowed to take tab Bilastine 20 mg OD whereas, patients of group B were allowed to take tab. Fexofenadine Hydrochloride 120 mg OD orally for two weeks. The baseline Total Nasal Symptom Score (TNSS) were compared between two groups. The study findings showed that the mean TNSS was significantly reduced in our study group. Baseline TNSS was 13.55 and 13.45 in Group A and Group B respectively. Reduction in this parameter first become apparent in the 24 hours and maintained till 2nd week. Bilastine showed significant improvement in quality of life of Allergic rhinitis patients and proved to be more effective than fexofenadine in reducing the TNSS score, when used alone in allergic rhinitis patient.

Neck Swelling After Sneezing

A 29-year-old, non-smoker male presented with a painless neck swelling with a sudden onset after a bout of violent sneezing two days ago. He had no other remarkable medical history except for seasonal allergic rhinitis for the past three years. He was referred for evaluation after being advised an antihistaminic drug for the relief of nasal symptoms. Bilateral crepitant swelling was found in the neck on physical examination.

Abstract 6382: Targeting mast cells restores T cell infiltration and sensitizes sarcomas to PD-L1 inhibition

Abstract Despite recent advances in cancer research, developments in sarcoma treatment have been slow. The efficacy of chemotherapy in sarcoma is limited by the pathophysiology of surrounding tumor stroma. Abnormalities in the tumor microenvironment (TME) result in stiffening of the tumor and accumulation of mechanical stresses which in turn cause the extreme deformation and collapse of intratumoral vessels. Strategies to induce TME reprogramming with the aim to restore mechanical properties of the tissue as well as tumor blood vessel functionality involve the use of “mechanotherapeutics”. Herein, we exploited the potential of the antihistamine drug and mast cell stabilizer, ketotifen, to induce mechanotherapeutic effects in murine models of soft tissue and bone sarcoma. Mast cells are the first population of immune cells drawn to the tumorigenic nidus where they interact with multiple components of the TME. Yet, their role in tumor stroma remains enigmatic as they either promote or inhibit tumor development depending on the conditions. In agreement with other mechanotherapeutics, we found that ketotifen induces vascular normalization in a dose dependent manner as indicated by the increase in perfusion, higher open lumen fraction and pericyte coverage of the vessels. Moreover, in vivo ultrasound shear wave elastography confirmed the mechanotherapeutic properties of ketotifen in reducing tissue stiffness, while further ex vivo validation indicated that TME reprogramming is mediated by a significant reduction in cancer associated fibroblast and inhibition of collagen synthesis as well as of that of other extracellular matrix components. Furthermore, we found that ketotifen modulates the immune microenvironment to promote immunostimulation. Immune stimulation was mediated by both intratumoral T cell accumulation and higher cytotoxic to regulatory T cell ratio concomitantly with a pronounced reduction in tissue hypoxia and upregulation of leukocyte adhesion molecules on endothelium. As a result of ketotifen-induced TME reprogramming, the addition of ketotifen to doxorubicin-aPDL1 combination treatment exhibited therapeutic superiority as opposed to doxorubicin-aPDL1, offering a durable tumor remission and immunological memory following tumor rechallenge experiments. Taken together, our findings demonstrate that ketotifen has a dual role in shaping the TME: i) reducing intratumoral physical forces to improve perfusion and ii) establishing favorable immunogenic conditions. Therefore, incorporating such agents in clinical practice holds great promise in the treatment of refractory, advanced sarcomas. Citation Format: Myrofora Panagi, Fotios Mpekris, Chrysovalantis Voutouri, Christina Michael, Anastasia Constantinidou, John D. Martin, Triantafyllos Stylianopoulos. Targeting mast cells restores T cell infiltration and sensitizes sarcomas to PD-L1 inhibition [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6382.

Abstract 6381: Superior effects of polymeric micelles in reprogramming tumor microenvironment and enhancing nano-immunotherapy

Abstract Nano-immunotherapy has high potential to improve cancer patient outcomes, as already demonstrated in triple negative breast cancer with the combination of nanoparticle albumin-bound paclitaxel and the immune checkpoint blocker antibody, atezolizumab. This regimen, however, does not lead to complete cure with median survival lasting less than two years. To increase patient survival, research focuses on repurposing common drugs to modulate the tumor microenvironment (TME), aiming to increase delivery of nanoparticles, antibodies and other drug regimens and improve immunostimulation. These drugs, however, exhibit certain dose-limitations and are associated with adverse effects. Here, taking advantage of the TME reprogramming capabilities of the approved antihistamine drug tranilast, we developed polymeric tranilast-loaded nanoparticles and explored their potential to modulate the TME more efficiently than the free drug. The results were striking as the micellar formulation of tranilast administered in a dose 100 times lower than that of the free drug reported superior reprogramming effects in two syngeneic triple negative breast tumor models. These effects were due to the enhanced intratumoral accumulation and cancer-associated fibroblast uptake of the nanoparticles compared to the free drug. Tranilast micelles were also found to promote significantly the delivery and efficacy of epirubicin micelles, overcome immune checkpoint resistance and induce tumor immunogenicity. Overall, the proposed micelles improved the efficacy of nano-immunotherapy in both breast cancer tumor models leading to complete cure. Furthermore, we employed the non-invasive and clinically applied ultrasound shear wave elastography method to monitor changes in tumor stiffness, which is the first effect caused by the tranilast micelles, and thus to determine an optimal dose-scheduling. Importantly, we found that tumor stiffness before the initiation of nano-immunotherapy was able to predict the efficacy of the treatment providing strong evidence for the potential of shear wave elastography to be used as a biomarker predictive of response. Our findings are very encouraging indicating that a) encapsulation of TME modulating drugs improves their pharmacokinetic properties, while allows for drastic reduction in the dose of administration, b) modulation of the TME can lead to complete cures of nano-immunotherapy in resistant to this therapy breast cancer tumor models, and c) ultrasound shear wave elastography can be employed for optimizing the use of TME modulating agents and for the prediction of tumor response to nano-immunotherapy allowing for optimized treatment protocols. Citation Format: Myrofora Panagi, Fotios Mpekris, Pengwen Chen, Chrysovalantis Voutouri, Yasuhiro Nakagawa, John D. Martin, Tetsuro Hiroi, Hiroko Hashimoto, Genichiro Ishii, Motohiro Kojima, Kazunori Kataoka, Horacio Cabral, Triantafyllos Stylianopoulos. Superior effects of polymeric micelles in reprogramming tumor microenvironment and enhancing nano-immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6381.

Loratadine, an antihistaminic drug, suppresses the proliferation of endometrial stromal cells by inhibition of TRPV2

The transient receptor potential (TRP) channel TRPV2 is widely expressed in a variety of different cell types and tissues. However, elucidating the exact biological functions of TRPV2 is significantly hampered by the lack of selective pharmacological tools to modulate channel activity in vitro and in vivo. This study aimed to identify new compounds that modify TRPV2 activity via the use of a plate-based calcium imaging approach to screen a drug repurposing library. Three antihistaminic drugs, loratadine, astemizole and clemizole were identified to reduce calcium-influx evoked by the TRPV2 agonist tetrahydrocannabivarin in HEK293 cells expressing murine TRPV2. Using single-cell calcium-microfluorimetry and whole-cell patch clamp recordings, we further confirmed that all three compounds induced a concentration-dependent block of TRPV2-mediated Ca2+ influx and whole-cell currents, with loratadine being the most potent antagonist of TRPV2. Moreover, this study demonstrated that loratadine was able to block both the human and mouse TRPV2 orthologs, without inhibiting the activity of other closely related members of the TRPV superfamily. Finally, loratadine inhibited TRPV2-dependent responses in a primary culture of mouse endometrial stromal cells and attenuated cell proliferation and migration in in vitro cell proliferation and wound healing assays. Taken together, our study revealed that the antihistaminic drugs loratadine, astemizole and clemizole target TRPV2 in a concentration-dependent manner. The identification of these antihistaminic drugs as blockers of TRPV2 may form a new starting point for the synthesis of more potent and selective TRPV2 antagonists, which could further lead to the unravelling of the physiological role of the channel.

Inflammatory immune-mediated adverse reactions induced by COVID-19 vaccines in previously injected patients with soft tissue fillers: A case series of 20 patients.

BackgroundAdverse events (AE) after COVID‐19 vaccines, particularly, but not solely, with those messenger RNA (mRNA)‐based vaccines, have rarely been reported in patients previously treated with dermal fillers (DF).ObjectiveTo evaluate the morphology, clinical characteristics, the timing of presentation, and outcomes of inflammatory AE appeared in patients injected with DF, after anti‐COVID‐19 vaccination.MethodsDescriptive study of a case series of 20 consecutive patients collected after the occurrence of AE in previously filled areas post COVID‐19 vaccination.ResultsFrom January 2021 to July 2021, we analyzed 20 AE reactions triggered by COVID‐19 vaccines in the previously mentioned cohort. They were vaccinated with Pfizer/Biontech (11; 55%), Moderna (5; 25%), Astra‐Zeneca (3; 15%), and Sputnik (1; 5%). The most common manifestations were oedema/swelling, angioedema, erythema, skin induration, and granuloma. Less common reactions included myalgia and lymphadenopathy. In 13/20 (65%) cases, the AE appeared after the first dose of vaccine. These inflammatory AE appeared more rapidly after the second dose than after the first one. In 13/20 (65%) cases, the symptomatology subsided with anti‐inflammatory/antihistaminic drugs, while spontaneously in 3/20 (15%). The manifestations are ongoing.in the remaining four cases (20%).ConclusionAlthough probably rare, both RNA‐based and adenovirus‐based anti‐COVID‐19 vaccines can cause inflammatory bouts in patients previously treated with DF. In these cases, caution should be paid on subsequent vaccine doses, considering a tailored risk/benefit for any case before next vaccination.

Characterising the evolution of antipsychotic polypharmacy and clozapine prescribing patterns in schizophrenia patients during psychiatric hospitalisations

IntroductionA high prevalence of antipsychotic polypharmacy (APP) and low utilisation of clozapine is considered as inappropriate prescribing that can lead to suboptimal treatment, increased risk of poor response or adverse effects.ObjectivesTo explore the evolution of prevalence of APP and associated factors as well as clozapine prescribing patterns between hospital admission and discharge.MethodsWe collected retrospective data on adult inpatients diagnosed with schizophrenia spectrum disorders in 2020-2021 in 6 Belgian hospitals.ResultsOf the 516 patients analysed, APP prescribing significantly increased from 47.9% on hospital admission to 59.1% at discharge. Both on admission and at discharge, APP was associated with treatment with a first-generation antipsychotic, not being treated with an antidepressant nor a mood stabilizer, high antipsychotic dosage, increased number of psychoactive cotreatments and total medicines. A lower number of comorbidities (OR=0.68, CI=0.50-0.91), no treatment with benzodiazepines (OR=0.02, CI=0.01-0.09) nor with trazodone or sedative antihistamines (OR=0.06, CI=0.01-0.03) and two or more previous antipsychotic trials (OR=4.91, CI=1.30-18.57) was associated with APP on admission only. APP at discharge was more frequent in patients with antipsychotic adverse effects (OR=2.57, CI=1.10-6.00), prior clozapine use (OR=16.30, CI=3.27-81.22) and not involuntary admitted (OR=0.26 CI=0.08-0.88). Contrary to admission, treatment with benzodiazepines was associated with APP at discharge (OR=10.9, CI=3.38-5.38). Only 9.3% of admitted patients were treated with clozapine. Although 28.1% were eligible, clozapine was introduced to 10 patients leading to 11% being discharged on it.ConclusionsInappropriate prescribing of antipsychotics to schizophrenia patients persist after psychiatric hospitalisations and are associated with identifiable characteristics.DisclosureNo significant relationships.

Editorial introductions.

Editorial introductions.

Efficacy of Rupatadine in Treatment of Chronic Idiopathic Urticaria

Introduction: Urticaria is a vascular lesion of the skin characterized by the appearance of well demarcated wheels along with angioedema. In more than 75% of cases, a causative agent can’t be established and thus is termed as chronic Idiopathic Urticaria. Treatment of this condition focuses on measures which provide symptomatic relief; 2nd and 3rd generation anti-histaminic drugs are the mainstays now for the treatment of chronic idiopathic urticaria. Objectives: To determine the efficacy of rupatadine in the treatment of chronic idiopathic urticaria. Materials and Methods: A clinical trial was conducted on 60 patients who were suffering from chronic idiopathic urticaria from March to August 2015 at Department of Dermatology and Venereology, Combined Military Hospital (CMH), Dhaka. Tab. Rupatadine 5 mg 1 tab daily was given for 6 weeks. Clinical response of treatment and adverse effect was assessed at every two weeks’ interval by taking history and clinical examination. Ethical issue was addressed Results: The patients reported a considerable improvement in overall chronic idiopathic urticaria due to the use of Rupatadine. The mean total symptom score (TSS) value reduced by 83% compared to the base line evaluation at the end of the therapy duration. Total disappearance of symptom was recorded in 25% patients. There were 79% decrease in the score for number of wheals, 81% reduction in the score for size of the wheals, 88% reduction in the pruritus severity score, and 83% reduction in the duration of pruritus score in relation to baseline evaluation. Conclusion: 5mg of Rupatadine once daily is effective in patients with chronic idiopathic urticaria. JAFMC Bangladesh. Vol 17, No 2 (December) 2021: 39-42

New Electrochemical Sensor Based on Hierarchical Carbon Nanofibers with NiCo Nanoparticles and Its Application for Cetirizine Hydrochloride Determination.

A new electrochemical sensor based on hierarchical carbon nanofibers with Ni and Co nanoparticles (eCNF/CNT/NiCo-GCE) was developed. The presented sensor may be characterized by high sensitivity, good electrical conductivity, and electrocatalytic properties. Reproducibility of its preparation expressed as %RSD (relative standard deviation) was equal to 9.7% (n = 5). The repeatability of the signal register on eCNF/CNT/NiCo-GCE was equal to 3.4% (n = 9). The developed sensor was applied in the determination of the antihistamine drug—cetirizine hydrochloride (CTZ). Measurement conditions, such as DPV (differential pulse voltammetry) parameters, supporting electrolyte composition and concentration were optimized. CTZ exhibits a linear response in three concentration ranges: 0.05–6 µM (r = 0.988); 7–32 (r = 0.992); and 42–112 (r = 0.999). Based on the calibration performed, the limit of detection (LOD) and limit of quantification (LOQ) were calculated and were equal to 14 nM and 42 nM, respectively. The applicability of the optimized method for the determination of CTZ was proven by analysis of its concentration in real samples, such as pharmaceutical products and body fluids (urine and plasma). The results were satisfactory and the calculated recoveries (97–115%) suggest that the method may be considered accurate. The obtained results proved that the developed sensor and optimized method may be used in routine laboratory practice.

Formulation of Ebastine Fast-Disintegrating Tablet Using Coprocessed Superdisintegrants and Evaluation of Quality Control Parameters.

Ebastine is a long-acting, nonsedating, second-generation antihistaminic drug that prevents histamine action, mainly in immediate hypersensitivity. This project was aimed to formulate and characterize orodispersible tablets of ebastine, utilizing different proportions of three disintegrants, namely crospovidone, sodium starch glycolate, and coprocessed superdisintegrant. Initially, fifteen trial batches of ebastine orodispersible tablets were outlined using the central composite design of Minitab software. The tablets were formulated by the direct compression method. The compressed tablets were then evaluated for precompression and postcompression physicochemical parameters, such as angle of repose, Carr's index, Hausner's ratio, hardness, thickness, weight variation, drug content, friability, wetting time, disintegration time, dispersion time, and water absorption ratio. The in vitro dissolution test was conducted according to Indian Pharmacopeia 2018, with the help of the rotating paddle method using 0.5% w/v sodium lauryl sulfate buffer in 0.1 N HCl. For the optimized batch (8th batch), all the physicochemical parameters like angle of repose (33.77°), Carr's index (19.34%), Hausner's ratio (1.24), weight variation (202.5 mg), hardness (4.3 kg/cm2), friability (0.44%), thickness (3.16 mm), dissolution (95.78%), and drug content (101.67%) were within the acceptable limit as per Indian Pharmacopeia 2018. The wetting time, disintegration time, dispersion time, and water absorption ratio were reported to be 25.1 seconds, 16.0 seconds, 38.6 seconds, and 91.92%, respectively. Hence, the results suggested that orodispersible tablets of ebastine can be formulated. Furthermore, the mixing of crospovidone, sodium starch glycolate, and coprocessed super disintegrants can result in excellent desirable properties in the orodispersible tablet.

Combined medical therapy in the treatment of allergic rhinitis: Systematic review and meta-analyses.

Antihistamines (ATH) and intranasal corticosteroids (INCS) are primary treatments for patients with allergic rhinitis (AR). When monotherapy of either primary treatment fails to control symptoms, combined medical therapy is an option. In this meta-analysis we assessed the additional effects of different medical combinations compared with primary treatments. Systematic searches on PubMed and EMBASE were updated on November 4, 2021. Randomized, controlled trials comparing the effects of combinations with monotherapy were included. There were 7 comparisons: (1) ATH-decongestant vs ATH; (2) ATH-leukotriene receptor antagonist (LTRA) vs ATH; (3) INCS-ATH vs INCS; (4) INCS-LTRA vs INCS; (5) INCS-decongestion vs INCS; (6) INCS-saline irrigation vs INCS; and (7) ATH-saline irrigation vs ATH. Data were pooled for meta-analysis. Outcomes were composite nasal symptom score, composite ocular symptom score, quality of life (QoL), and adverse events. Fifty-three studies were included. Compared with ATH alone, the ATH-decongestant combination improved composite nasal symptoms; ATH-LTRA improved nasal symptoms in patients with perennial AR; and ATH-nasal saline improved both symptoms and QoL. Compared with INCS alone, the INCS-intranasal ATH combination improved nasal symptoms, ocular symptoms, and QoL; INCS-LTRA improved ocular symptoms but not nasal symptoms; and INCS-nasal saline improved QoL but not symptoms. There were no additional effects observed from adding oral ATH or topical decongestant to INCS. After ATH monotherapy fails to control symptoms, addition of decongestant, saline, or LTRA can improve the outcomes. When INCS monotherapy is ineffective, addition of intranasal ATH can improve nasal symptoms; LTRA can improve ocular symptoms, and saline irrigation can improve QoL.

Preparation of Sepestan Anti-cough Syrup and Comparison of its Effectiveness With Diphenhydramine Syrup in Treating Cough in Children With Upper Respiratory Tract Infection: A Double-blind Randomized Clinical Trial

Background and Objectives Antihistamine drugs for acute upper respiratory tract infection treatment in children have many side effects. In this study, a anti-cough syrup was prepared from Cordia (Sepestan in Persian) extract and its effect was compared to that of diphenhydramine syrup on cough relief of children with upper respiratory tract infection. Subjects and Methods This double-blind randomized clinical trial was conducted on 124 children with upper respiratory tract infection aged 6-12 years referred to Abouzar Hospital in Ahvaz, Iran during 2019- 2021 in two treatment groups. The first group was given Sepestan syrup at a dose of 20 mg/kg/day and the second group received diphenhydramine syrup at a dose of 5 mg/kg/day in four dosages. For three days, the number and severity of day-time and night-time coughs were examined and the data were analyzed with independent t-test and chi-square test in SPSS software, version 24. Results The number and severity of day-time and night-time coughs in the group received Sepestan syrup significantly decreased compared to the diphenhydramine group, without any side effects (P&lt;0.001). Conclusion High polysaccharides, strong antioxidants, and anti-inflammatory compounds of Sepestan can reduce throat irritation and soften the chest. The mucilage in the Sepestan extract can dissolve in water and produce a viscous substance such as gelatin that cause softening of the breast and expectoration.

Biomarkers of PEGylated Liposomal Doxorubicin-Induced Hypersensitivity Reaction in Breast Cancer Patients Based on Metabolomics.

This study aimed to analyze and discuss the biomarkers of PEGylated liposomal doxorubicin (PLD) injection-induced hypersensitivity reactions (HSRs) in advanced breast cancer patients. Fourteen patients from Sun Yat-sen Memorial Hospital were included in the study between April 15th, 2020 and April 14th, 2021. Patient plasma was collected 30 min before PLD injection. HSRs were found to occur in a total of 9 patients (64.3%). No association was found between HSRs and various patient characteristics such as age, body surface area, anthracycline treatment history, IgE, and complement 3 and 4 (p > 0.05). Non-targeted metabolomics analysis of patient plasma was performed, and several metabolites showed significant association with HSRs. In particular, l-histidine (fold change = 91.5, p = 0.01) showed significantly higher levels in the immediate HSR group, while myristicin (fold change = 0.218, p = 0.003), urocanic acid (fold change = 0.193, p = 0.007), and d-aldose (fold change = 0.343, p = 0.003) showed significantly lower levels in the same group. In vivo experiments showed that exogenous histidine aggravated HSRs and increased IgE plasma levels in rats following the injection of PLD. Histidine can be decarboxylated to histamine by histidine decarboxylase. Histidine decarboxylase inhibitor 4-bromo-3-hydroxybenzoic acid improved symptoms and IgE levels in vivo. These findings suggested that l-histidine can be a potential biomarker for PLD-induced HSR. Moreover, an antihistamine drug, histidine decarboxylase inhibitor, or dietary histidine management could be used as potential preventive measures. Furthermore, metabolomics research could serve as a powerful method to explore biomarkers or uncover mechanisms of drug side effects.