Sustained Delivery of Olopatadine from Vitamin-E Loaded Contact Lenses.

Purpose: Topical antihistamines, such as olopatadine hydrochloride, an H1 receptor antagonist, are commonly prescribed for treating allergic conjunctivitis. Drug delivery via eye drops has many deficiencies including a short residence time due to tear drainage via the nasolacrimal duct, which results in a low bioavailability and potential for side effects. These deficiencies could be mitigated by a drug-eluting contact lens such as the recently approved ACUVUE® THERAVISION™ WITH KETOTIFEN which is a daily disposable etafilcon, a drug-eluting contact lens with ketotifen (19 µg per lens). Here, we investigate the feasibility of designing a drug-eluting lens with sustained release of olopatadine for treating allergies using an extended wear lens. Methods: Nanobarrier depots composed of vitamin-E (VE) are formed through direct entrapment by ethanol-driven swelling. The drug-loaded lenses are characterized for transparency and water content. In vitro release is measured under sink conditions and fitted to a diffusion control release model to determine diffusivity and partition coefficient. Results: In vitro studies indicate that ACUVUE OASYS® and ACUVUE TruEye™ lenses loaded with ∼0.3 g of VE/g of hydrogel effectively prolong olopatadine dynamics by 7-fold and 375-fold, respectively. Incorporation of VE into the lenses retains visible light transmission and other properties. Conclusion: The VE incorporation in commercial lenses significantly increases the release duration offering the possibility of antiallergy extended wear lenses.

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.

Protective effect of olopatadine hydrochloride against LPS-induced acute lung injury: via targeting NF-κB signaling pathway.

BACKGROUND: Morbidity and mortality rates associated with acute lung injury/acute respiratory distress syndrome (ALI/ARDS) are high (30-40%). Nuclear factor-kappa B (NF-κB) is a transcription factor, associated with transcription of numerous cytokines leading to cytokine storm, and thereby, plays a major role in ALI/ARDS and in advanced COVID-19 syndrome. METHODS: Considering the role of NF-κB in ALI, cost-effective in silico approaches were utilized in the study to identify potential NF-κB inhibitor based on the docking and pharmacokinetic results. The identified compound was then pharmacologically validated in lipopolysaccharide (LPS) rodent model of acute lung injury. LPS induces ALI by altering alveolar membrane permeability, recruiting activated neutrophils and macrophages to the lungs, and compromising the alveolar membrane integrity and ultimately impairs the gaseous exchange. Furthermore, LPS exposure is associated with exaggerated production of various proinflammatory cytokines in lungs. RESULTS: Based on in silico studies Olopatadine Hydrochloride (Olo), an FDA-approved drug was found as a potential NF-κB inhibitor which has been reported for the first time, and considered further for the pharmacological validation. Intraperitoneal LPS administration resulted in ALI/ARDS by fulfilling 3 out of the 4 criteria described by ATS committee (2011) published workshop report. However, treatment with Olo attenuated LPS-induced elevation of proinflammatory markers (IL-6 and NF-κB), oxidative stress, neutrophil infiltration, edema, and damage in lungs. Histopathological studies also revealed that Olo treatment significantly ameliorated LPS-induced lung injury, thus conferring improvement in survival. Especially, the effects produced by Olo medium dose (1 mg/kg) were comparable to dexamethasone standard. CONCLUSION: In nutshell, inhibition of NF-κB pathway by Olo resulted in protection and reduced mortality in LPS- induced ALI and thus has potential to be used clinically to arrest disease progression in ALI/ARDS, since the drug is already in the market. However, the findings warrant further extensive studies, and also future studies can be planned to elucidate its role in COVID-19-associated ARDS or cytokine storm.

Exploration of efficacy and mechanism of 0.05% cyclosporine eye drops (II) monotherapy in allergic conjunctivitis-associated dry eye.

PURPOSE: To explore the efficacy and relevant mechanism of 0.05% cyclosporine A (CsA) eye drops (II) monotherapy in patients with allergic conjunctivitis-associated dry eye (ACDE). METHODS: Prospective, randomized, controlled study. Fifty-three patients with mild-to-moderate ACDE were randomly assigned to two groups. The CsA group received 0.05% CsA eye drops (II) monotherapy four times daily. The control group received 0.1% olopatadine twice daily combined with 0.1% preservative-free artificial tears four times daily. Clinical symptoms and signs, tear total IgE, and lymphotoxin-α (LT-α) concentrations were assessed at pre- and post-treatment days 7, 30, and 60. And we further measured six tear cytokines levels using a microsphere-based immunoassay. RESULTS: The CsA group showed significant improvement in symptoms (Ocular Surface Disease Index and itching scores) and signs (conjunctival hyperaemia, conjunctival oedema, conjunctival papillae, tear break-up time (TBUT), corneal fluorescein staining, and goblet cell density) at each follow-up period compared to pre-treatment (all P < 0.050). And its improvement in itching scores (P7th < 0.001, P30th = 0.039, and P60th = 0.031) and TBUT (P7th = 0.009, P30th = 0.003, and P60th = 0.005) was more significant than the control group at all follow-up periods. The tear total IgE, interleukin (IL)-5, IL-6, periostin, eotaxin-3, and MMP-9 levels significantly decreased in the CsA group at day 60 after treatment (all P < 0.050). And the changed values in tear total IgE were positively correlated with the change in itching scores. CONCLUSIONS: 0.05% CsA eye drops (II) monotherapy can rapidly improve the symptoms and signs, especially in ocular itching and TBUT, in patients with ACDE. And its efficacy is superior to 0.1% olopatadine combined with artificial tears. Moreover, CsA downregulates the expression levels of tear inflammatory cytokines, including tear total IgE, IL-5, IL-6, periostin, eotaxin-3, and MMP-9. Among that, the reduction in tear total IgE levels may reflect the improvement of ocular itching.

UV spectrophotometric methods for simultaneous determination of ketorolac tromethamine and olopatadine hydrochloride: Application of multiple standard addition for assay of ophthalmic solution.

Ophthalmic preparations that contain ketorolac tromethamine (KET) and olopatadine HCl (OLO) are used to relieve seasonal allergies and allergic conjunctivitis. Simultaneous quantification of KET and OLO was held by validated and simple spectrophotometric methods. KET was determined directly from the fundamental UV absorption spectra (at 323 nm), while OLO was determined after performing either dual wavelength or ratio derivative methods. The first method was based on measuring the absorbance difference (ΔA) between 243 and 291 nm, while the second depended on generating first derivative ratio spectra using 3.0 µg/mL KET as a divisor and measuring OLO responses at 234 nm (minima). Multiple standard addition method was applied to enable the determination of OLO which is considered as the weakly absorbing species as well as the minor component in a challenging dosage form ratio (4:1). The linearity ranges of the developed methods were 3-12 µg/mL and 4-40 µg/mL for KET and OLO, respectively. Simultaneous determination of both drugs was successfully implemented to lab prepared eye drops that contain KET, OLO and benzalkonium chloride as an inactive ingredient. Greenness assessment indicates minimal impact on environment. The developed methods determined the cited drugs with % recovery ± SD of 99.63 ± 0.01 for KET, 100.90 ± 0.02 and 100.31 ± 0.01 for OLO using dual wavelength and first derivative ratio methods, respectively. Using F-test and t-test at confidence level %95 to compare between the results of the presented methods and a reported method show no significant difference which allows precise, accurate, rapid, and simple quantification of quality control samples that contain KET and OLO.

Assessment of the efficacy of olopatadine 0.1% in the treatment of vernal keratoconjunctivitis in terms of clinical improvement based on total ocular symptom score and ocular surface disease index.

Purpose: The main objective of this study is to explore the efficacy of olopatadine 0.1% treatment in the resolution of symptoms of vernal keratoconjunctivitis (VKC) among the Indian population. Methods: This single-center, prospective cohort study involved 234 patients with VKC. Patients were treated with olopatadine 0.1%, twice daily for a period of 12 weeks and then followed up in 1st week, 4th week, 3rd month, and 6th month. The extent of relief in the symptoms of VKC was measured using total ocular symptom score (TOSS) and ocular surface disease index (OSDI). Results: In the present study, the dropout rate was 5.6%. Total of 136 males and 85 females with a mean age of 37.68 ± 11.35 years completed the study. TOSS score reduced from 58.85 to 5.06 and the OSDI score reduced from 75.41 to 11.2 with statistical significance (P < 0.01) from 1st week to 6th week after olopatadine 0.1% treatment. The data showed relief in subjective symptoms of itching, tearing, and redness, and relief in discomfort in functions related to ocular grittiness, visuals like reading, and environmental like tolerability in dry conditions. Further, olopatadine 0.1% was effective in both males and females, and patients across ages 18-70 years. Conclusion: Based on TOSS and OSDI scores, the findings of this study validate safety and tolerability as revealed by low adverse effects and moderate efficacy of olopatadine 0.1% in reducing VKC symptoms in a broader age group (18-70 years) of both genders.

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.

Understanding ocular comfort differences between 0.7% olopatadine and 0.3% pheniramine maleate/0.025% naphazoline hydrochloride eye drops.

CLINICAL RELEVANCE: This study found 0.7% olopatadine (Pataday Once Daily Relief Extra Strength) eye drops to provide better initial comfort than 0.3% pheniramine maleate/0.025% naphazoline hydrochloride (VISINE® Allergy Eye Relief Multi-Action Antihistamine and Redness Reliever) eye drops suggesting that patients may comply better with the Pataday than VISINE. BACKGROUND: To compare the ocular comfort at instillation of Pataday and VISINE allergy eye drops. METHODS: Minimally symptomatic participants were recruited based upon Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire scores (≤3 units); they also had minimal between-eye inter-ocular comfort differences as judged by visual analogue scale scores (VAS; ≤7 units). Baseline comfort was evaluated by eye with a VAS. One drop of Pataday or VISINE was then applied to the right eye with the alternative drop being applied to the left eye. The same VAS evaluated comfort by eye at drop instillation, and then at 30 seconds, 1 minute, and 2 minutes post-instillation. Drop experience was also evaluated with Likert questions. LogMAR visual acuities and bulbar conjunctival redness were evaluated pre- and post-drop instillation. RESULTS: A total of 159 participants were recruited (mean ± SD age = 26.2 ± 7.5). The VAS found that eyes treated with Pataday were significantly more comfortable at instillation than eyes treated with VISINE. Likert questions indicated that participants significantly preferred Pataday drops compared to the VISINE drops at instillation with regards to overall eye comfort, eye stinging, eye burning, and foreign body sensation. There were no between drop differences in visual acuity, though eyes treated with VISINE were less red than eyes treated with Pataday. CONCLUSIONS: Topically applied Pataday drops were more comfortable than VISINE drops.

Determining initial ocular comfort differences between 0.7% olopatadine and 0.035% ketotifen fumarate.

PURPOSE: To compare the ocular comfort at application of topical, over-the-counter, 0.7% olopatadine and 0.035% ketotifen fumarate anti-allergy eye drops. METHODS: This study recruited participants who were minimally symptomatic based upon Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire scores (≤3 units) and who had minimal between-eye inter-ocular comfort differences as judged by visual analog scale scores (VAS; ≤7 units). Baseline comfort was evaluated by eye with a VAS. One drop of 0.7% olopatadine or 0.035% ketotifen fumarate was then applied to the right eye with the alternative drop being immediately applied to the left eye. Participants were next evaluated with the same comfort VAS by eye at drop application, and then at 30 s, 1 min, and 2 min post-application. LogMAR visual acuities and bulbar conjunctival redness were evaluated pre- and post-drop application to judge initial changes. RESULTS: This study enrolled 159 participants who had a mean ± SD age of 26.3 ± 7.7 years, and 78.6% of the participants were female. The VAS found that the 0.7% olopatadine drop was more comfortable than the 0.035% ketotifen fumarate drop at all time-points. There were no between-eye differences in LogMAR visual acuities, yet bulbar redness was significantly less in 0.7% olopatadine treated eyes compared 0.035% ketotifen fumarate treated eyes. CONCLUSION: This study found that topically applied 0.7% olopatadine drops were initially more comfortable than 0.035% ketotifen fumarate drops.

Intranasal Olopatadine-Mometasone in the Treatment of Seasonal Allergic Rhinitis.

OBJECTIVE: To review the pharmacology, efficacy, and safety of intranasal olopatadine hydrochloride-mometasone furoate (OM) combination in the treatment of seasonal allergic rhinitis (SAR). DATA SOURCES: The PubMed database and ClinicalTrials.gov were searched using the following terms: mometasone + olopatadine, GSP301, mometasone furoate, and olopatadine hydrochloride. STUDY SELECTION AND DATA EXTRACTION: Articles published in English between January 1987 and August 2022 related to pharmacology, safety, and clinical trials were assessed. DATA SYNTHESIS: In 2 phase II clinical trials, twice-daily (BID) and once-daily (QDay) intranasal OM demonstrated significant improvements in reflective total nasal symptom score (rTNSS) (BID P < 0.001 and QDay P < 0.001) and instantaneous total nasal symptom score (iTNSS) (BID P < 0.001 and P < 0.0001; QDay P < 0.001 and P < 0.0001). In 2 phase III clinical trials, BID OM showed significant improvements in rTNSS vs. placebo (P < 0.001), olopatadine monotherapy (P = 0.03 and P = 0.003), and mometasone monotherapy (P = 0.02 and P = 0.059). RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: OM is indicated for treatment of SAR symptoms. Caution with use must be considered for certain high-risk patients, existing tuberculosis; fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex. Due to its quick and sustained onset of action, OM may be an ideal agent for initial treatment of moderate-severe SAR for patients 12 years and older. CONCLUSION: OM significantly improves SAR symptoms and is a viable treatment option in short-term SAR.

Intranasal combo: fixed-dose combination of mometasone furoate and olopatadine hydrochloride in therapeutic strategies for rhinosinusitis.

A novel strategy for the treatment of allergic rhinitis results from the innovative combination of antihistamine and intranasal corticosteroid drugs. By combining two preparations with different mechanism of action, this novel approach facilitates quick and effective controls of all upper respiratory tract allergy symptoms. The article presents the results of a study of olopatadine hydrochloride and mometasone furoate fixed-dose combination (GSP301) administered intranasally from a spray formulation, with an attempt at positioning the treatment within the ARIA and EPOS guidelines.

Efficacy and safety of GSP301 nasal spray in children aged 6 to 11 years with seasonal allergic rhinitis.

BACKGROUND: GSP301 nasal spray is a fixed-dose combination of the antihistamine olopatadine hydrochloride and the corticosteroid mometasone furoate. OBJECTIVE: To evaluate the efficacy, safety, and tolerability of GSP301 in pediatric patients (aged ≥6 to <12 years) with seasonal allergic rhinitis (SAR). METHODS: This double-blind, randomized, parallel-group study randomized 446 eligible patients 1:1 (GSP301 [olopatadine hydrochloride 665 µg and mometasone furoate 25 µg] or placebo) as 1 spray/each nostril twice daily for 14 days. The primary end point was change from baseline in average morning and evening subject-reported 12-hour reflective Total Nasal Symptom Score (rTNSS) over a 14-day treatment period analyzed using mixed-effect model repeated measures. Additional assessments included instantaneous Total Nasal Symptom Score, Pediatric Rhinoconjunctivitis Quality of Life Questionnaire, reflective Total Ocular Symptoms Score, instantaneous Total Ocular Symptoms Score, individual symptoms, Physician-assessed Nasal Symptom Score, and adverse events. RESULTS: GSP301 showed clinically meaningful and statistically significant improvement in rTNSS vs placebo (-0.6; 95% confidence interval, -0.9 to -0.2; P = .001). Statistically significant improvements favoring GSP301 were shown for all individual rTNSS symptoms, instantaneous Total Nasal Symptom Score, and most of its individual symptoms, Physician-assessed Nasal Symptom Score (P = .01), and Pediatric Rhinoconjunctivitis Quality of Life Questionnaire (P < .001). For ocular symptoms, numerical improvements favoring GSP301 were observed, with statistical significance achieved only for reflective "tearing/watering eyes" (P = .04). Treatment-emergent adverse events occurred in 12.0% and 10.4% of patients in the GSP301 and placebo groups, respectively. One subject (0.5%) (placebo group) experienced a serious adverse event (suspected viral meningitis) that was not related to the study treatment and was resolved. CONCLUSION: GSP301 was well tolerated and efficacious for treating SAR symptoms in pediatric patients and showed a favorable safety profile. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03463031.

The Bladder Microbiome, Metabolome, Cytokines, and Phenotypes in Patients with Systemic Lupus Erythematosus.

Emerging studies reveal unique bacterial communities in the human bladder, with alteration of composition associated to disease states. Systemic lupus erythematosus (SLE) is a complex autoimmune disease that is characterized by frequent impairment of the kidney. Here, we explored the bladder microbiome, metabolome, and cytokine profiles in SLE patients, as well as correlations between microbiome and metabolome, cytokines, and disease profiles. We recruited a group of 50 SLE patients and 50 individually matched asymptomatic controls. We used transurethral catheterization to collect urine samples, 16S rRNA gene sequencing to profile bladder microbiomes, and liquid chromatography-tandem mass spectrometry to perform untargeted metabolomic profiling. Compared to controls, SLE patients possessed unique bladder microbial communities and increased alpha diversity. These differences were accompanied by differences in urinary metabolomes, cytokines, and patients' disease profiles. The SLE-enriched genera, including Bacteroides, were positively correlated with several SLE-enriched metabolites, including olopatadine. The SLE-depleted genera, such as Pseudomonas, were negatively correlated to SLE-depleted cytokines, including interleukin-8. Alteration of the bladder microbiome was associated with disease profile. For example, the genera Megamonas and Phocaeicola were negatively correlated with serum complement component 3, and Streptococcus was positively correlated with IgG. Our present study reveals associations between the bladder microbiome and the urinary metabolome, cytokines, and disease phenotypes. Our results could help identify biomarkers for SLE. IMPORTANCE Contrary to dogma, the human urinary bladder possesses its own unique bacterial community with alteration of composition associated with disease states. Systemic lupus erythematosus (SLE) is a complex autoimmune disease often characterized by kidney impairment. Here, we explored the bladder microbiome, metabolome, and cytokine profiles in SLE patients, as well as correlations between the microbiome and metabolome, cytokines, and disease profiles. Compared to controls, SLE patients possessed a unique bladder microbial community and elevated alpha diversity. These differences were accompanied by differences in bladder metabolomes, cytokines, and patients' disease profiles. SLE-enriched genera were positively correlated with several SLE-enriched metabolites. SLE-depleted genera were negatively correlated to SLE-depleted cytokines. Alteration of the bladder microbiome was associated with disease profile. Thus, our study reveals associations between the bladder microbiome and the bladder metabolome, cytokines, and disease phenotypes. These results could help identify biomarkers for SLE.

Green Liquid Chromatography Method for the Determination of Related Substances Present in Olopatadine HCl Nasal Spray Formulation, Robustness by Design Expert.

BACKGROUND: Dual therapeutic nature drug mast cell stabilizer and histamine receptor antagonist olopatadine hydrochloride (OPT) nasal spray does not have an official monograph, and no literature is available. Eye drops formulation had the official monograph for impurities, but the determination was done in two methods. OBJECTIVE: A simple and effective green liquid chromatography method to develop and validate for the related substances of OPT nasal spray formulation. METHOD: A 25 min gradient method was employed to separate impurities and OPT with a 1.0 mL/min flow rate using a Boston green C8 (150 mm × 4.6 mm, 5 µm) HPLC column. The set wavelength and column oven temperatures were 299 nm and 30°C, respectively. pH 3.5 phosphate buffer-acetonitrile in the ratio of (70:30, v/v) as mobile phase A and (50:50, v/v) ratio as mobile phase B. A Quality by Design (QbD) based Design of Experiments (DoE) was employed to evaluate the robustness characteristics of the analytical method validation. RESULTS: The obtained RSD from the precision and intermediate precision was 0.4 to 4.1%. The % recovery of the impurities from LOQ to 150% of specification level was 87.5 to 110.3%. The linear regression curves for the impurities with a correlation coefficient of >0.999 indicate that all peak responses are linear with the concentration. The sample and standard solutions were stable for 24 h at benchtop and refrigerator conditions. CONCLUSIONS: All the critical peaks were well separated from the forced degradation studies' diluent, placebo, and generated degradation peaks. The method validation data and QbD based robustness study results indicate that the developed impurities method fits the routine quality control laboratory use. National Environmental Index (NMEI), Green Analytical Procedure Index (GAPI), Analytical Eco-scale and Analytical Greenness (AGREE) tools expressed the method's greenness. HIGHLIGHTS: The proposed method is QbD utilized and green chemistry assessed impurities determination method for OPT in nasal spray formulation.

A Quality by Design and green LC technique for the determination of mast cell stabilizer and histamine receptor antagonist (Olopatadine HCl) in multiple formulations.

Mast cell stabilizer and histamine receptor antagonist olopatadine hydrochloride (OPT) assay method predicated on LC have been established for the analysis in multiple formulations. The current method dealt with ophthalmic solution, nasal spray, and tablet formulation products. The isocratic chromatography method was optimized and validated with a Boston green C8 column (150 × 4.6 mm, 5 µm i.d.). Sodium dihydrogen phosphate buffer (pH 3.5) with acetonitrile in the ratio of 75:25 (v/v) was used as a mobile phase at a flow rate of 1.0 mL min-1 and at the column temperature of 30°C, and the detection was done at 299 nm. The method was validated as per International Council for Harmonisation (ICH) guidelines and United States Pharmacopoeia (USP). The accuracy results ranged from 99.9 to 100.7%, % relative standard deviation (RSD) from the precision was 0.5, and correlation coefficient from the linearity experiment was > 0.999. Solution stability was established for 24 h at room temperature and refrigerator conditions, and it was found that the solutions were stable. Using quality by design-based experiment designs, critical quality attributes were studied and it was found that the method was robust. In all the forced degradation studies peak purity was passed, and no interference was found at the retention time of the active component. The method validation data demonstrated that the developed method is linear, precise, accurate, specific, robust, and stable for the determination of OPT from multiple formulations. Analytical eco-scale tool, Green Analytical Procedure Index (GAPI) tool, and the National Environmental Method Index (NEMI) were used to evaluate the greenness of the method, and the analytical eco-score of 77 for the presented method was found to be excellent.

Ophthalmic drugs: in vitro paraoxonase 1 inhibition and molecular docking studies.

Glaucoma is a neuropathy disorder and is generally treated by drugs. Allergic conjunctivitis is a common ophthalmologic disease. Paraoxonase 1 (PON1) is an organophosphate hydrolyzer and antiatherogenic enzyme. PON1 is known for preventing atherosclerosis through lipid-modifying features, as well as which has decisive actions of antiapoptosis, anti-inflammatory, antithrombosis, and antiadhesion antioxidant activity properties. Thus, reducing the enzyme levels in hyperthyroidism, chronic renal failure, glaucoma, diabetes mellitus, and cardiovascular diseases is a significant risk. This study was tested some ophthalmic drugs used to treat the diseases, such as glaucoma and allergic conjunctivitis, mentioned above, travoprost, latanoprost, ketotifen, emedastine, and olopatadine, for their inhibition activities against PON1. These drugs displayed the potent inhibition effect with IC50 values ranging between 14.95 ± 0.15 and 299.60 ± 4.07 µM and KI constants ranging from 9.71 ± 2.63 to 261.50 ± 59.98 µM. Besides, the molecular docking analyses of the competitive inhibitors, travoprost, emedastine, and olopatadine, were performed to understand the binding interactions on the enzyme's binding site. According to both in vitro and in silico analysis results, travoprost had the most potent effect on PON1 enzyme activity.

Efficacy and safety of twice-daily olopatadine-mometasone combination nasal spray (GSP301) in the treatment of allergic rhinitis: a systematic review and meta-analysis.

PURPOSE: GSP301 is a fixed-dose combination of olopatadine hydrochloride (antihistamine) and mometasone furoate (corticosteroid). This meta-analysis aims to evaluate the efficacy and safety of GSP301 in the treatment of allergic rhinitis. METHODS: A systematic review and meta-analysis were conducted. The data were collected from PubMed, Cochrane Central Register of Controlled Trials and Embase databases till June 2021. In patients with AR, short-term (2/6 weeks) and long-term (52 weeks) effects of GSP301 were assessed. Average morning and evening 12-h reflective total nasal symptom score (rTNSS), instantaneous total nasal symptom score (iTNSS), reflective total ocular symptom score (rTOSS), instantaneous total ocular symptom score(iTOSS), Physician-assessed nasal symptom score (PNSS), rhinoconjunctivitis quality of life (RQLQ), rhinitis control assessment test (RCAT) and adverse events (AEs) were measured. RESULTS: Five randomized controlled trials were included. GSP301 showed greatly improvement in rTNSS (MD = - 0.99; [95% CI - 1.19 to - 0.79]; P < 0.01; I2 = 0), iTNSS (MD = - 1.05; [95% CI - 1.44 to - 0.67]; P < 0.01; I2 > 50%), rTOSS (MD = - 0.50; [95% CI - 0.72 to - 0.29]; P < 0.01; I2 = 0), iTOSS (MD = - 0.64; [95% CI - 1.02 to - 0.26]; P < 0.01; I2 > 50%), PNSS (MD = - 1.01; [95% CI - 1.32 to - 0.69]; P < 0.01; I2 = 22.13%), RQLQ (MD = - 0.43; [95% CI - 0.57 to - 0.30]; P < 0.01; I2 = 0%) and RCAT (MD = 1.94; [95% CI 1.43-2.45]; P < 0.01; I2 = 0%) in the short term. No statistical difference was observed in the outcome of long-term PNSS, RQLQ and RCAT. CONCLUSION: GSP301 is a safe and well-tolerated medication. It showed short-term benefits for seasonal and perennial AR, but may not help to improve patients' quality of life and rhinitis control in the long run.

H1-Receptor Antagonist Olopatadine Inhibits MUC5AC Secretion by Conjunctival Goblet Cells.

The study examined the effect of H1-receptor antagonist olopatadine on the secretory function of cultured rat conjunctival goblet cells (CGC) assessed by enzyme-linked lectin assay employing UEA-I lectin. The level of mRNA for membrane-bound protein MUC16 in histaminestimulated CGC was assayed by reverse transcription PCR in the control and after preliminary application of olopatadine. The intracellular calcium concentration [Ca2+]i was measured by the calcium colorimetric method using GENMED kits. The effects of histamine and olopatadine on p-ERK level were assessed by Western blotting. Histamine up-regulated secretion of mucin MUC5AC and expression of membrane-bound protein MUC16 in CGC. In addition, it increased both [Ca2+]i and the level of phosphorylated ERK. These effects were diminished by preliminary application of olopatadine that probably acted via the ERK signaling pathway. Thus, olopatadine reduced [Ca2+]i and down-regulated ERK phosphorylation by binding to H1-receptors, thereby inhibiting secretion of mucin from histamine-stimulated CGC.

Environmental exposure unit simulates natural seasonal birch pollen exposures while maximizing change in allergic symptoms.

BACKGROUND: Birch pollen is a prevalent aeroallergen during the springtime allergy season. In field studies, variable allergen exposure and environmental factors can affect data quality while environmental exposure units (EEUs) deliver controlled, standardized, and reproducible allergen exposures. OBJECTIVE: To inform study design for EEU trials evaluating antiallergic therapies. METHODS: In this prospective study, 76 participants with birch allergy experienced 3 exposures to birch pollen: (1) an out-of-season EEU challenge (two 3-hour sessions on consecutive days); (2) a natural seasonal exposure; and (3) an in-season EEU challenge (3-hour exposure for 2 weeks after birch pollen season initiation). RESULTS: The total nasal symptom score, total ocular symptom score, and total symptom score (TSS = total nasal symptom score plus total ocular symptom score) were assessed every 30 minutes and daily during EEU and natural exposures. A high association between TSSs and day 2 of the out-of-season and in-season EEU challenges was noted, with a good association between the maximum TSS during the natural and in-season EEU challenges, and natural season and day 2 of the out-of-season EEU challenge (P < .001 for all). Participants had higher maximum change from the baseline TSS during day 2 of the out-of-season EEU challenge (12.4) vs the following: (1) first day (9.8); (2) in-season EEU challenge (8.4); and (3) natural seasonal exposure (7.6) (P < .001 for all). CONCLUSION: A strong association was seen between the presence of allergy symptoms and exposure to birch pollen in the EEU (maximum change in symptom scores during day 2) and in the field. A hybrid trial design may be useful to demonstrate the clinical efficacy of novel antiallergic therapies requiring fewer participants and shorter timelines and expediting treatment availability.