Pharmacological interventions for pediatric obstructive sleep apnea (OSA): Network meta-analysis.

IMPORTANCE: Pediatric obstructive sleep apnea (OSA) is a common disease that can have significant negative impacts on a child's health and development. A comprehensive evaluation of different pharmacologic interventions for the treatment of OSA in children is still lacking. OBJECTIVE: This study aims to conduct a comprehensive systematic review and network meta-analysis of pharmacological interventions for the management of obstructive sleep apnea in pediatric population. DATA SOURCES: PubMed, Web of Science, Embase, The Cochrane Library, and CNKI were searched from 1950 to November 2022 for pediatric OSA. STUDY SELECTION: Multiple reviewers included Randomized controlled trials (RCTs) concerning drugs on OSA in children. DATA EXTRACTION AND SYNTHESIS: Multiple observers followed the guidance of the PRISMA NMA statement for data extraction and evaluation. Bayesian network meta-analyses(fixed-effect model) were performed to compare the weighted mean difference (WMD), logarithmic odds ratios (log OR), and the surface under the cumulative ranking curves (SUCRA) of the included pharmacological interventions. Our protocol was registered in PROSPERO website (CRD42022377839). MAIN OUTCOME(S) AND MEASURE(S): The primary outcomes were improvements in the apnea/hypopnea index (AHI), while secondary outcomes included adverse events and the lowest arterial oxygen saturation (SaO2). RESULTS: 17 RCTs with a total of 1367 children with OSA aged 2-14 years that met the inclusion criteria were eventually included in our systematic review and network meta-analysis. Ten drugs were finally included in the study. The results revealed that Mometasone + Montelukast (WMD-4.74[95%CrIs -7.50 to -2.11], Budesonide (-3.45[-6.86 to -0.15], and Montelukast(-3.41[-5.45 to -1.39] exhibited significantly superior therapeutic effects compared to the placebo concerning apnea hypopnea index (AHI) value with 95%CrIs excluding no effect. Moreover, Mometasone + Montelukast achieved exceptionally high SUCRA values for both AHI (85.0 %) and SaO2 (91.0 %). CONCLUSIONS AND RELEVANCE: The combination of mometasone furoate nasal spray and oral montelukast sodium exhibits the highest probability of being the most effective intervention. Further research is needed to investigate the long-term efficacy and safety profiles of these interventions in pediatric patients with OSA.

Allergic Rhinitis: A Review.

Importance: Allergic rhinitis affects an estimated 15% of the US population (approximately 50 million individuals) and is associated with the presence of asthma, eczema, chronic or recurrent sinusitis, cough, and both tension and migraine headaches. Observations: Allergic rhinitis occurs when disruption of the epithelial barrier allows allergens to penetrate the mucosal epithelium of nasal passages, inducing a T-helper type 2 inflammatory response and production of allergen-specific IgE. Allergic rhinitis typically presents with symptoms of nasal congestion, rhinorrhea, postnasal drainage, sneezing, and itching of the eyes, nose, and throat. In an international study, the most common symptoms of allergic rhinitis were rhinorrhea (90.38%) and nasal congestion (94.23%). Patients with nonallergic rhinitis present primarily with nasal congestion and postnasal drainage frequently associated with sinus pressure, ear plugging, muffled sounds and pain, and eustachian tube dysfunction that is less responsive to nasal corticosteroids. Patients with seasonal allergic rhinitis typically have physical examination findings of edematous and pale turbinates. Patients with perennial allergic rhinitis typically have erythematous and inflamed turbinates with serous secretions that appear similar to other forms of chronic rhinitis at physical examination. Patients with nonallergic rhinitis have negative test results for specific IgE aeroallergens. Intermittent allergic rhinitis is defined as symptoms occurring less than 4 consecutive days/week or less than 4 consecutive weeks/year. Persistent allergic rhinitis is defined as symptoms occurring more often than 4 consecutive days/week and for more than 4 consecutive weeks/year. Patients with allergic rhinitis should avoid inciting allergens. In addition, first-line treatment for mild intermittent or mild persistent allergic rhinitis may include a second-generation H1 antihistamine (eg, cetirizine, fexofenadine, desloratadine, loratadine) or an intranasal antihistamine (eg, azelastine, olopatadine), whereas patients with persistent moderate to severe allergic rhinitis should be treated initially with an intranasal corticosteroid (eg, fluticasone, triamcinolone, budesonide, mometasone) either alone or in combination with an intranasal antihistamine. In contrast, first-line therapy for patients with nonallergic rhinitis consists of an intranasal antihistamine as monotherapy or in combination with an intranasal corticosteroid. Conclusions and Relevance: Allergic rhinitis is associated with symptoms of nasal congestion, sneezing, and itching of the eyes, nose, and throat. Patients with allergic rhinitis should be instructed to avoid inciting allergens. Therapies include second-generation H1 antihistamines (eg, cetirizine, fexofenadine, desloratadine, loratadine), intranasal antihistamines (eg, azelastine, olopatadine), and intranasal corticosteroids (eg, fluticasone, triamcinolone, budesonide, mometasone) and should be selected based on the severity and frequency of symptoms and patient preference.

The impact of nasal use of azelastine and mometasone furoate on drug-induced sleep endoscopy.

OBJECTIVE: Endoscopic evaluation becomes difficult when excessive secretion/hypersalivation occurs in the upper airway. Intranasal corticosteroids and antihistamines reduce symptoms of rhinorrhea and nasal congestion. For this reason, in our study, we aimed to examine the effects of mometasone furoate and azelastine on both the amount of secretion and upper airway obstruction in terms of possible benefits during drug-induced sleep endoscopy (DISE). PATIENTS AND METHODS: A total of 92 patients participated in the study [69 (75%) were males and 23 (25%) were females]. Three groups in Group 1 used intranasal mometasone furoate for 30 days, Group 2 used intranasal azelastine for 30 days, and Group 3 did not use any nasal spray for 30 days. Then, DISE was performed on all patients on the 30th day. Upper airway obstructions detected in DISE were interpreted according to the VOTE classification. Furthermore, the amount of secretion and patients' tolerance levels observed during DISE were also assessed. RESULTS: Multilevel obstruction was detected in 94.5% of all patients participating in the study. Tolerance was poor in 18 (19.5%) of the patients participating in the study. Better DISE tolerance was determined in the female gender. DISE tolerance was also better in underweight and normal-weight patients (BMI < 25). CONCLUSIONS: This study first investigated nasal mometasone furoate and azelastine on DISE. This study showed that prior use of nasal mometasone furoate or azelastine before DISE did not affect the amount of secretion, tolerance level, severity, and configuration of obstruction.

Management of pediatric choanal atresia restenosis and subglottic stenosis using steroid-eluting stents.

OBJECTIVES: To depict the novel use of steroid-eluting stents in the treatment of choanal atresia (CA) restenosis and subglottic stenosis (SGS). METHODS: A retrospective chart review of three pediatric patients, one with CA and two with SGS, treated with mometasone furoate eluting mini stents (PROPEL) was performed. Patients were evaluated for restenosis and adverse events between one to twelve months postoperatively. RESULTS: Postoperatively, patient one with CA showed no signs of restenosis and required no further intervention. Patient two with SGS demonstrated an open subglottic lumen with no signs of restenosis as well as improved phonation following his planned serial procedures. Post-operatively, patient three with SGS exhibited no restenosis of the subglottic lumen, tolerated intermittent tracheostomy capping, and demonstrated improved phonation. CONCLUSION: In this case series, we outline successful treatments for the management of CA restenosis and SGS with mometasone furoate-eluting stents. To our knowledge, this is the first reported application of this treatment in pediatric patients with CA restenosis and the second reported application in pediatric patients with SGS.

Maximal medical treatment of adenoid hypertrophy: a prospective study of preschool children.

PURPOSE: This study aimed to examine the effectiveness of the combined maximal medical treatment for adenoid hypertrophy in preschool children. METHODS: Sixty-four children underwent one-year combined therapy with intranasal mometasone furoate, oral desloratadine, nasal saline irrigation, and bacteriotherapy. Additionally, decongestion drops were applied during scheduled breaks. RESULTS: Of the 64 treated children, 72% showed clinical improvement in adenoid symptoms while 28% did not improve and underwent surgery. These groups differed significantly in terms of the overall reduction in ailments after treatment (p < 0.001), infection rate (p < 0.001), catarrh severity (p < 0.001) and nasal patency (p < 0.001). Endoscopic examination confirmed that responders experienced, on average, a decrease of 8.4% in the adenoid/choana ratio and an improvement in mucosal coverage of the adenoid. These effects were not observed in the group of children whose parents opted for surgery after nine months of conservative treatment. CONCLUSIONS: The proposed new schema of long-term maximal medical treatment with the use of combined intermittent treatment of intranasal mometasone furoate and decongestion drops, oral desloratadine, nasal saline irrigation, and bacteriotherapy can be attempted in patients with adenoid hypertrophy symptoms, and responders may avoid the need for surgery. The applied treatment breaks resulted in a low number of therapeutic side effects.

[Clinical and pathological analysis of 345 cases of vulvar lichen sclerosus and a preliminary study on the frequency of maintenance treatment].

Objective: To analyze and summarize the clinical and pathological characteristics, management, and efficacy of patients with vulvar lichen sclerosus (VLS) through a single center large sample study, and preliminarily to explore the frequency of maintenance treatment medication for VLS. Methods: The clinical data of VLS patients in Obstetrics and Gynecology Hospital of Fudan University from 2018 to 2021 were retrospectively collected. The clinicopathological characteristics (patients' age, course of disease, complicated disease history, family history, symptoms, signs and pathology), treatment and effects were retrospectively analyzed. The patients in the maintenance treatment stage were followed up regularly to explore the minimum frequency of individual medication to maintain the stability of the disease. Results: (1) General situation: a total of 345 patients with VLS were included in this study. The average age was (50.4±14.7) years (ranged from 8 to 84 years old), prevalence was highest in the 50-59 years group (30.1%, 104/345). Immune diseases occurred in 18.6% (33/177) of patients, 24.3% (43/177) of patients had allergic skin diseases, and 5.6% (10/177) of the patients' immediate family members had chronic vulvar pruritus or vulvar hypopigmentation. (2) Clinical features: the most common symptom was vulvar pruritus (96.1%, 196/204) among 204 patients with recorded symptoms. The most common sign was hypopigmentation of the vulva (96.3%, 206/214). The most common involved sites were labia minora (70.3%, 142/202), labia majora (67.8%, 137/202), and labial sulcus (59.4%, 120/202). The cumulative number of sites involved in 62 vulvar atrophy patients (2.7±1.1) was significantly higher than that in 152 non-atrophy patients (2.2±1.0; t=3.48, P=0.001). The course of vulvar atrophy was (9.3±8.5) years, which was significantly longer than that of non-atrophy patients [(6.6±5.6) years; t=2.04, P=0.046]. (3) Pathological features: among the 286 patients with electronic pathological sections, the most common pathological feature in the epidermis was epithelial nail process passivation (71.3%, 204/286). The common pathological features in the dermis were interstitial collagenization (84.6%, 242/286), and inflammatory cell infiltration (73.8%, 211/286). (4) Treatment: 177 patients received standardized treatment after diagnosis and were followed up regularly in our hospital. In the initial treatment stage, 26.0% (46/177) of the patients were treated with 0.05% clobetasol propionate cream, and 74.0% (131/177) of the patients were treated with 0.1% mometasone furoate ointment. The complete remission rates of the two methods were respectively 80.4% (37/46) and 74.0% (97/131), and there was no statistically significant difference (χ²=0.76, P=0.385). During maintenance treatment, 27.1% (48/177) of the patients took the medication twice a week, 35.0% (62/177) took the medication once a week, and 37.9% (67/177) took the medication once every 10 days. During follow-up after 6 months of maintenance treatment, there were no patients with recurrence of pruritus or progression of vulvar signs. Conclusions: The majority of VLS patients have itching, hypopigmentation, involvement of labia minora and labia majora, progressive atrophy, and inflammatory infiltration of dermis. Local treatments of mometasone furoate and clobetasol propionate have good initial therapeutic effects. The frequency exploration of individualized maintenance treatment could minimize the occurrence of adverse reactions when ensuring the stability of the patients' condition.

Steroid-Eluting Implants: An Adjunctive Therapy After Double-Stage Laryngotracheal Reconstruction.

OBJECTIVES: The primary objective is to describe a case in which a steroid-eluting implant was utilized to help prevent postoperative granulation and restenosis in a patient who underwent double-stage laryngotracheal reconstruction (dsLTR) for subglottic stenosis. METHODS: This case presents a 3-year-old female who underwent dsLTR with anterior cartilage graft placement and posterior sagittal split for subglottic stenosis. A silicone stent was placed at the time of the dsLTR. After stent removal, direct laryngoscopy and bronchoscopy (DLB) was performed at 4 to 5 week intervals. These visits revealed a significant amount of supraglottic and glottic edema, and granulation tissue at the proximal aspect of the graft contributing to airway obstruction and restenosis. This was treated twice with CO2 laser excision, balloon dilation, and triamcinolone injection. On the third treatment with these modalities, a mometasone furoate implant was inserted as an adjunctive therapy. The implant was inserted to lateralize the vocal folds, prevent webbing, and to extend to the narrowed area within the subglottis to prevent granulation and restenosis. These same treatments were repeated at the fourth visit with another mometasone furoate implant of a smaller size placed in the same location. RESULTS: Findings on DLB since treatment with the steroid-eluting implants have shown persistent granulation tissue limited to the tracheostomy stoma site. Treatments with CO2 laser, balloon dilation, and triamcinolone injection have continued, with occasional use of silver nitrate cautery at the external stoma site. There has not been any significant evidence of edema, granulation, or stenosis in the glottis or subglottis to require another steroid-eluting implant. CONCLUSIONS: Steroid-eluting implants appear to be a safe and effective adjunctive therapy in the routine surveillance of pediatric patients with a tracheostomy who have undergone dsLTR. They may help combat granulation formation and restenosis seen in some dsLTR patients.

Resolution of hypoalbuminemia in a 3-year-old hound-mix dog after discontinuation of oclacitinib.

OBJECTIVE: Albumins are protein molecules that account for 50% of total plasma protein. They are imperative in maintaining intravascular colloidal oncotic pressure, act as key scavenger molecules for oxygen free radicals, and perform a major role in transporting numerous substances and in wound healing. Hypoalbuminemia has been reported as the consequence of decreased intake, increased loss, decreased production, and redistribution. While anecdotal evidence of tyrosine kinase inhibitors causing hypoalbuminemia in canine patients exists, to the author's knowledge there is no formal report to this effect to date. This case report aims to bridge the gap between anecdotal evidence and literature. ANIMAL: 3-year-old neutered male hound-mix canine. CLINICAL PRESENTATION, PROGRESSION, AND PROCEDURES: The patient was presented for recurrent otitis externa refractory to treatments with orbifloxacin/mometasone/posaconazole otic suspension, miconazole/polymyxin B/prednisolone otic suspension, ketoconazole/TrizEDTA, and gentamicin/mometasone/clotrimazole, which prompted consideration of oral antifungals. Baseline blood work prior to initiation of fluconazole showed elevated alkaline phosphatase. Treatment was initiated with fluconazole, and blood work was rechecked and revealed hypoalbuminemia. Multiple diagnostic tests failed to reveal a cause of hypoalbuminemia. TREATMENT AND OUTCOME: Discontinuation of oclacitinib that the patient was being administered resulted in normalization of serum albumin. CLINICAL RELEVANCE: It is unclear whether hypoalbuminemia associated with oclacitinib administration is associated with worse outcomes for pathologies in canine patients; however, this seems to be the case in humans according to some reports. This report aims to take a step in the direction of this knowledge.

Multi-Gram Scale Synthesis and Characterization of Mometasone Furoate EP Impurity C.

Mometasone furoate is a synthetic corticosteroid used in the treatment of skin inflammatory conditions, hay fever and asthma. The industrial manufacturing routes to mometasone furoate are generally accompanied by the formation of numerous process impurities that need to be detected and quantified, as requested by regulatory authorities. The ready availability of such impurities in the required quantity and purity is therefore essential for toxicological studies, analytical method development and process validation. Herein, we report the multi-gram scale preparation of 21'-chloro-(16'α-methyl-3',11',20'-trioxo-pregna-1',4'-dien-17'-yl)-furan-2-carboxylate (mometasone furoate EP impurity C), one of the known impurities of mometasone furoate. This study also includes the systematic investigation of the final acylation step, as well as the characterization of the difuroate enol ether intermediate and its conversion to the target impurity C.

Development of Niosomal Vesicles Loaded Mometasone Furoate Gel for Transdermal Delivery and its Evaluation.

BACKGROUND: Mometasone Furoate (MF) is a corticosteroid (glucocorticoid) used to treat eczema, psoriasis, allergies, and rash on the skin; also used to reduce itching, redness, and swelling (inflammation). It has been reported that the bioavailability of MF is less than 11% when given via the nasal route. Encapsulating the drug in niosomes can improve the active pharmaceutical ingredient's bioavailability by enhancing both physical and biological stability. OBJECTIVE: The goal of the study is to develop, a non-ionic surfactant-based vesicular system, by loading mometasone furoate, and introducing it into a gel-based formulation by utilizing an appropriate gelling agent, and performing its evaluation. METHODS: The niosome vesicle was prepared by vacuum rotary evaporation method (Thin film hydration method). Gel was prepared using the dispersion method and in-vitro drug diffusion studies using Franz-diffusion cells. RESULTS: According to the results of the experiments conducted for the study, Mometasone Furoate niosomal gel was prepared utilizing Mometasone Furoate niosomes that were made using the thin film hydration process, Cholesterol, and Span 60, and loaded in various amounts of Carbopol as a geling agent. The niosomes' zeta potential was found to be -24 mV, showing that the formulation is stable. The polydispersity index (PDI) was found to be 0.409 and the average size of niosomes to be 252.7 nm. The performance of the gel of the optimized formulations containing 2% Carbopol showed in vitro diffusion for 7 hours and an increased flux rate as compared to the plain MF. CONCLUSION: The experiments carried out during the study led to the conclusion that the thin-film hydration method was suitable for the formation of the MF-niosomes by using Span 60 and Cholesterol (2:1). The gel formulation containing 2% Carbopol indicated better in vitro diffusion following the Higuchi model across all niosomal gel formulations. Niosomal gel can be regarded as the best vesicular carrier for the efficient distribution of mometasone furoate via the transdermal route.

Meta-analysis and cost-effectiveness analysis of intranasal corticosteroid treatment in allergic rhinitis with ocular symptoms.

BACKGROUND: Intranasal corticosteroid (INCS) has a beneficial effect on ocular symptoms in allergic rhinitis (AR). To our knowledge, the cost-effectiveness of available INCS for AR with ocular symptoms is yet to be demonstrated. OBJECTIVE: To evaluate the cost-effectiveness of INCSs including Budesonide (BANS), Mometasone furoate (MFNS), Triamcinolone (TANS), and Fluticasone furoate (FFNS) on ocular symptoms associated with AR in the Thai context. METHODS: The percentage of effectiveness in improving total ocular symptoms score (TOSS) was derived from the result of a meta-analysis that estimated the SMD of each INCS treatment compared to placebo as clinical input parameters. A cost-effectiveness analysis based on a decision-tree model to assess one-year costs and outcomes from a Thai societal perspective. The outcomes were to compare incremental cost-effectiveness ratio (ICER). Probabilistic sensitivity analyses (PSA) were also conducted to capture parameter uncertainties. RESULTS: 13 eligible RCTs with a total of 3,722 patients with SAR were included in the analysis. The percentage of effectiveness of FFNS, MFNS, TANS, and BANS was 59.89%, 45.60%, 24.89%, and 16.00%, respectively. The ICER of FFNS, MFNS, and TANS is THB-6,539.92, 4,593.83, and 1,401.24 compared to BANS. CECA result showed the probability of using FFNS is considered cost-effective in 87.50% of cases from zero value followed by MFNS (0.80%), TANS (5.40%), and BANS (6.30%). With a threshold greater than THB20,000, FFNS is considered a cost-effective strategy. CONCLUSIONS: FFNS is a cost-effective option compared to alternative INCSs in Thailand for treating AR with ocular symptoms.

Nasal Absorption Enhancement of Mometasone Furoate Nanocrystal Dispersions.

Purpose: We designed a 0.05% mometasone furoate (MF) nanocrystal dispersion and investigated whether the application of MF nanocrystals in nasal formulations enhanced local absorption compared to traditional nasal MF formulations (CA-MF). Methods: MF nanocrystal dispersions (MF-NPs) were prepared by bead milling MF microcrystal dispersions (MF-MPs) consisting of MF, 2-hydroxypropyl-ß-cyclodextrin, methylcellulose, and purified water. Pluronic F-127 combined with methylcellulose, Pluronic F-68, or carbopol was used as a base for in situ gelation (thickener). MF concentrations were measured using high-performance liquid chromatography, and nasal absorption of MF was evaluated in 6 week-old male Institute of Cancer Research (ICR) mice. Results: The particle size range of MF prepared with the bead mill treatment was 80-200 nm, and the nanoparticles increased the local absorption of MF, which was higher than that of CA-MF and MF-MPs. In addition, unlike the results obtained in the small intestine and corneal tissue, the high absorption of nanocrystalline MF in the nasal mucosa was related to a pathway that was not derived from energy-dependent endocytosis. Moreover, the application of the in situ gelling system attenuated the local absorption of MF-NPs, owing to a decrease in drug diffusion in the dispersions. Conclusion: We found that nanoparticulation of MF enhances local intranasal absorption, and nasal bioavailability is higher than that of CA-MF. In addition, we demonstrate that viscosity regulation is an important factor in the design of nasal formulations based on MF nanocrystals. These findings provide insights for the design of novel nanomedicines with enhanced nasal bioavailability.

Vitamin D supplementation improves the therapeutic effect of mometasone on allergic rhinitis.

This study aimed to investigate the efficacy and safety of vitamin D supplementation in the treatment of allergic rhinitis (AR) using mometasone. A total of 140 patients with moderate and severe AR treated at our hospital between January 2017 and August 2020 were recruited as subjects for this study. The patients were randomly divided into control and experimental groups, with 70 patients in each group. Mometasone nasal spray was used in both groups, and vitamin D was administered to the experimental group for four weeks. The total nasal symptom scores (TNSS) and rhinoconjunctivitis quality of life questionnaire (RQLQ) were used to assess the efficacy of treatment. T lymphocyte subsets (CD3+, CD4+ and CD8+) and serum anti-inflammatory and proinflammatory cytokines such as interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) were analyzed. The incidence of adverse reactions was recorded. Serum vitamin D levels were lower in patients with AR. After 4 weeks of treatment, total TNSS scores, T lymphocyte subsets (CD3+, CD4+), CD4+/CD8+ ratio, TNF-α, and total RQLQ scores were significantly reduced compared to the initial testing (P<0.05) in the two groups; CD8+, IFN-γ, and IL-10 levels as well as serum vitamin D were significantly increased compared to the initial test (P<0.05). The improvement in these parameters in the experimental group was significantly greater than that in the control group (P<0.05), except for sneezing and eye symptoms in the TNSS and RQLQ scores. It was concluded that vitamin D supplementation improves the therapeutic effect of mometasone nasal spray on AR and is thus recommended as an adjuvant therapy for moderate and severe AR.

Porous silicon embedded in a thermoresponsive hydrogel for intranasal delivery of lipophilic drugs to treat rhinosinusitis.

Intranasal delivery is the most preferred route of drug administration for treatment of a range of nasal conditions including chronic rhinosinusitis (CRS), caused by an infection and inflammation of the nasal mucosa. However, localised delivery of lipophilic drugs for persistent nasal inflammation is a challenge especially with traditional topical nasal sprays. In this study, a composite thermoresponsive hydrogel is developed and tuned to obtain desired rheological and physiochemical properties suitable for intranasal administration of lipophilic drugs. The composite is comprised of drug-loaded porous silicon (pSi) particles embedded in a poloxamer 407 (P407) hydrogel matrix. Mometasone Furoate (MF), a lipophilic corticosteroid (log P of 4.11), is used as the drug, which is loaded onto pSi particles at a loading capacity of 28 wt%. The MF-loaded pSi particles (MF@pSi) are incorporated into the P407-based thermoresponsive hydrogel (HG) matrix to form the composite hydrogel (MF@pSi-HG) with a final drug content ranging between 0.1 wt% to 0.5 wt%. Rheomechanical studies indicate that the MF@pSi component exerts a minimal impact on gelation temperature or strength of the hydrogel host. The in-vitro release of the MF payload from MF@pSi-HG shows a pronounced increase in the amount of drug released over 8 h (4.5 to 21-fold) in comparison to controls consisting of pure MF incorporated in hydrogel (MF@HG), indicating an improvement in kinetic solubility of MF upon loading into pSi. Ex-vivo toxicity studies conducted on human nasal mucosal tissue show no adverse effect from exposure to either pure HG or the MF@pSi-HG formulation, even at the highest drug content of 0.5 wt%. Experiments on human nasal mucosal tissue show the MF@pSi-HG formulation deposits a quantity of MF into the tissues within 8 h that is >19 times greater than the MF@HG control (194 ± 7 µg of MF/g of tissue vs. <10 µg of MF/g of tissue, respectively).

[Control of hormonal rhinitis symptoms in patients with hypothyrosis: pathogenetic and clinical aspects]. / Kontrol' simptomov khronicheskogo rinita u patsientov s gipotireozom: patogeneticheskie i klinicheskie aspekty.

BACKGROUND: One of the poorly studied sections of the pathology of ENT organs is chronic rhinitis in patients with hypothyroidism, the pathogenesis of which has not been fully understood, the diagnosis causes significant difficulties, and there are no recommendations for treatment. Despite receiving replacement therapy with levothyroxine, the symptoms of rhinitis persist. OBJECTIVE: To study the effectiveness of the use of intranasal glucocorticosteroids in patients with chronic rhinitis and hypothyroidism. MATERIAL AND METHODS: Patients with chronic rhinitis and hypothyroidism used mometasone nasal spray 100 mcg 1 time per day for a course of treatment of 2 months (n=60). To assess the symptoms of rhinitis, a visual analog scale (0-10 points), endoscopic examination of ENT organs, anterior active rhinomanometry were used. Evaluation of mucociliary transport was used a saccharin test. The concentration of transforming growth factor (TGF-ß1) in nasal secretion and blood serum was studied by ELISA (Enzyme-Linked Immunosorbent Assay), the number of metabolites of NO - nitrites+nitrates (NOx) was recorded by colorimetric method. RESULTS: The use of mometasone nasal spray in patients with hypothyroidism helped to reduce complaints on a visual-analog scale (difficulty in nasal breathing, rhinorrhea) and improve nasal breathing according to anterior active rhinomanometry. The concentrations of TGF-ß1 and NOx in nasal secretions before mometasone treatment were higher than after treatment, which probably indicates the contribution of these substances to the formation of edematous hypertrophic changes from the nose in patients with hypothyroidism.

Sensitivity of Pharmacokinetics to Differences in the Particle Size Distribution for Formulations of Locally Acting Mometasone Furoate Suspension-Based Nasal Sprays.

To assess bioequivalence of locally acting suspension-based nasal sprays, the U.S. FDA currently recommends a weight-of-evidence approach. In addition to in vitro and human pharmacokinetic (PK) studies, this includes a comparative clinical endpoint study to ensure equivalent bioavailability of the active pharmaceutical ingredient (API) at the site of action. The present study aimed to assess, within an in vitro/in vivo correlation paradigm, whether PK studies and dissolution kinetics are sensitive to differences in drug particle size for a locally acting suspension-based nasal spray product. Two investigational suspension-based nasal formulations of mometasone furoate (MF-I and MF-II; delivered dose: 180 µg) differed in API particle size and were compared in a single-center, double-blind, single-dose, randomized, two-way crossover PK study in 44 healthy subjects with oral charcoal block. Morphology-directed Raman spectroscopy yielded volume median diameters of 3.17 µm for MF-I and 5.50 µm for MF-II, and dissolution studies showed that MF-II had a slower dissolution profile than MF-I. The formulation with larger API particles (MF-II) showed a 45% smaller Cmax and 45% smaller AUC0-inf compared to those of MF-I. Systemic bioavailability of MF-I (2.20%) and MF-II (1.18%) correlated well with the dissolution kinetics, with the faster dissolving formulation yielding the higher bioavailability. This agreement between pharmacokinetics and dissolution kinetics cross-validated both methods and supported their use in assessing potential differences in slowly dissolving suspension-based nasal spray products.

Plackett-Burman and face-centered composite designs for development and optimization of chromatographic method for the simultaneous determination of glycopyrronium, indacaterol and mometasone in their fixed dose combination inhaler - Green profile assessment.

A novel simple, specific, sensitive, accurate and precise reversed phase high performance liquid chromatographic method (RP-HPLC/UV) was developed and validated for the simultaneous estimation of Glycopyrronium bromide (GLY), Indacaterol acetate (IND) and Mometasone furoate (MOF) in pure form, in laboratory prepared mixtures and in pharmaceutical dosage form. Experimental design methodology was applied by using Plackett-Burman and face-centered composite designs to achieve the best resolution with minimum experimental trials. The designed model was statistically analyzed, graphically presented by surface plots and the relationships between coefficients of the derived polynomial equations were interpreted. Chromatographic separation was achieved on Inertsil ODS C18 column (250 ×4.6 mm, 5 µm) at ambient temperature using a mobile phase composed of methanol: 0.1% glacial acetic acid (pH4) in a gradient elution at a flow rate 1 mL /min. UV detection was carried out at 233 nm. Response was found to be linear in the concentration range of 20-120 µg /mL with regression coefficient (r2 = 0.999) for GLY, 50-300 µg /mL with regression coefficient (r2 = 0.9995) for IND and 50-300 µg /mL with regression coefficient (r2 = 0.9998) for MOF. The method was validated as per ICH guidelines and satisfactory results were achieved. The method was successfully applied for the analysis of the cited drugs in their fixed dose combination (FDC) pharmaceutical formulation. Statistical comparison between the results obtained by the proposed method and the reference methods for GLY, IND and MOF showed no significant difference. The developed method could be implemented in quality control aspects of the cited drugs. Four green metrics were used to evaluate the new RP-HPLC/UV method's greenness and compare it to other published techniques.

Pharmacokinetics of Nasal Esketamine in Patients with Allergic Rhinitis with and Without Nasal Decongestant Pretreatment and in Healthy Subjects with and Without Nasal Corticosteroid Pretreatment.

BACKGROUND AND OBJECTIVES: Nasal esketamine is indicated for the treatment of adults with treatment-resistant depression and depressive symptoms in adults with major depressive disorder with acute suicidal ideation or behavior. Primary objectives of this study were to evaluate the effect of nasal decongestant pretreatment in patients with allergic rhinitis and the impact of daily nasal corticosteroid administration by healthy subjects on nasal esketamine pharmacokinetics. METHODS: Patients with allergic rhinitis self-administered 56 mg of nasal esketamine after pretreatment with nasal oxymetazoline (0.05%) at 1 h before esketamine and without oxymetazoline pretreatment. They were exposed to grass pollen in an allergen challenge chamber to induce allergic rhinitis symptoms at approximately 2 h before each esketamine administration until 1 h after. Healthy subjects self-administered esketamine (56 mg) before and after administration for 16 consecutive days of mometasone (200 µg), with the second esketamine dose administered 1 h after the last mometasone dose. The plasma pharmacokinetics of esketamine and noresketamine were assessed after each esketamine administration. The tolerability of esketamine, including effects on dissociative and potential psychotomimetic symptoms and level of sedation and suicidal ideation and behavior, was evaluated. RESULTS: The rate of esketamine absorption was slightly greater in patients exhibiting symptoms of allergic rhinitis (decrease in median tmax from 32 min to 22 min). Increases in esketamine Cmax and AUC were also small (mean, ≤ 21%). The pharmacokinetics of esketamine was not affected by oxymetazoline or mometasone pretreatment. Esketamine was well tolerated when it was administered with or without pretreatment of oxymetazoline or mometasone. CONCLUSIONS: Patients exhibiting symptoms of rhinitis may receive nasal esketamine spray without dose adjustment. In addition, esketamine may be administered 1 h after using a nasal decongestant or corticosteroid. TRIAL REGISTRATION: The study was registered in the Clinical Trials (NCT02154334) and EudraCT (2014-000534-38) registries.

Zein nanoparticles as oral carrier for mometasone furoate delivery.

Mometasone furoate (MF) is a synthetic glucocorticoid used clinically to treat specific inflammatory disorders including superior and inferior respiratory tract. Due to its poor bioavailability we further investigated whether nanoparticles (NPs) made of zein protein may constitute a safe and effective choice to incorporate MF. Thus, in this work, we loaded MF into zein NPs aiming to evaluate possible advantages that could result from oral delivery and extend the range of MF application such as inflammatory gut diseases. MF-loaded zein NPs presented an average size in the range of 100 and 135 nm, narrow size distribution (polydispersity index < 0.300), zeta potential of around + 10 mV and association efficiency of MF over 70%. Transmission electron microscopy imaging revealed that NPs had a round shape and presented a smooth surface. The zein NPs showed low MF release in a buffer that mimics the gastric condition (pH = 1.2) and slower and controlled MF release in the intestinal condition (pH = 6.8). The short and intermediate safety of zein NPs was confirmed assessing the incubation against Caco-2 and HT29-MTX intestinal cells up to 24 h. Permeability studies of MF across Caco-2/HT29-MTX co-culture monolayer evidenced that zein NPs modulated MF transport across cell monolayer resulting in a stronger and prolonged interaction with mucus, potentially extending the time of absorption and overall local and systemic bioavailability. Overall, zein NPs showed to be suitable to carry MF to the intestine and future studies can be developed to investigate the use of MF-loaded zein NPs to treat intestinal inflammatory diseases.

Intranasal corticosteroid and antihistamine combinations in the treatment of allergic rhinitis: the role of the novel formulation olopatadine/mometasone furoate.

INTRODUCTION: Allergic rhinitis (AR) is a common disease with an important impact on the quality of life and very high management costs. In many patients, the poor control of rhinitis symptoms often requires the use of different drugs, and polytherapy tends to reduce therapeutic adherence. According to the latest version of ARIA guidelines, the currently recommended drugs for the treatment of moderate-to-severe AR are second-generation antihistamines, intranasal corticosteroids, and their combination, even in a single nasal spray device. A single medication with a rapid onset of action, acting on breakthrough symptoms too, would be advantageous, also in terms of patient compliance. AREAS COVERED: GSP301 (olopatadine 600 µg - mometasone furoate 25 µg) is a novel intranasal formulation, combining the second-generation antihistamine olopatadine hydrochloride with mometasone furoate. Here, we review the evidence for GSP301, especially concerning the efficacy and safety profile of this intranasal combination in the treatment of AR. EXPERT OPINION: The evidence provided in the current review clearly supports the use of GSP301 as a novel intranasal corticosteroid/antihistamine combination with a well-documented efficacy and safety profile in terms of rapid symptom relief and good tolerability.