Mometasone 25micrograms/dose / Olopatadine 600micrograms/dose nasal spray

The recent approval of the nasal spray combination of mometasone (MOM) and olopatadine (OLO) presents a significant analytical challenge, as only a single reported method exists for its determination, deviating from eco-friendly practices. This study addresses this critical gap by pioneering the application of machine learning techniques to develop robust UV spectrophotometric approach for the simultaneous quantification of MOM and OLO, along with two genotoxic impurities: 4-dimethylamino pyridine (DAP) and methyl para-toluene sulfonate (MTS). By simultaneously determining these highly concerning genotoxic impurities and active pharmaceutical ingredients, this method underscores its paramount significance in upholding rigorous pharmaceutical quality standards and safeguarding patient safety. Applying the multilevel-multifactor experimental design, the calibration set was meticulously chosen at five different concentrations, yielding 25 calibration mixtures with central levels of 4, 46.5, 2.5, and 3 µg/mL for MOM, OLA, MTS, and DAP, respectively. The key innovation lies in the strategic implementation of the Kennard-Stone Clustering Algorithm to create a robust validation set of thirteen mixtures, resolving the limitations of reported chemometric methods' random data splitting. This approach ensures unbiased evaluation across the full concentration space, improving the method's reliability and sustainability. The robustness of this approach was rigorously tested using five distinct chemometric models: principal component regression, classical least squares, partial least squares, genetic algorithm-partial least squares, and multivariate curve resolution-alternating least squares, demonstrating its broad applicability across diverse modeling techniques. All models successfully determined all components with excellent recovery, low bias-corrected prediction, and adequate limits of detection. The Greenness Index Spider Charts and the Green Solvents Selection Tool were used to choose environmentally conscious solvents. A comprehensive sustainability assessment employed six state-of-the-art tools, including the national environmental method index, complementary green analytical procedure index, analytical greenness metric, blue applicability grade index, carbon footprint analysis, and the red-green-blue 12 metrics. Favorable results across all metrics affirmed the method's eco-friendliness, real-world applicability, and cost-effectiveness, supporting sustainable development goals in pharmaceutical quality control processes.

Abstract licence: CC BY-NC-ND

BACKGROUND: GSP301 nasal spray is a fixed-dose combination of olopatadine hydrochloride (antihistamine) and mometasone furoate (corticosteroid). OBJECTIVE: To evaluate the efficacy and safety of GSP301 in patients with seasonal allergic rhinitis (SAR). METHODS: In this double-blind study, eligible patients (≥12 years of age) with SAR were randomized 1:1:1:1 to twice-daily GSP301 (665 μg of olopatadine and 25 μg of mometasone), olopatadine (665 μg), mometasone (25 μg), or placebo for 14 days. The primary end point-mean change from baseline in average morning and evening 12-hour reflective Total Nasal Symptom Score (rTNSS)-was analyzed via a mixed-effect model repeated measures (P < .05 was considered to be statistically significant). Additional assessments included average morning and evening 12-hour instantaneous TNSS (iTNSS), ocular symptoms, individual symptoms, onset of action, quality of life, and adverse events (AEs). RESULTS: A total of 1176 patients were randomized. GSP301 provided statistically significant and clinically meaningful rTNSS improvements vs placebo (least squares mean difference, -1.09; 95% CI, -1.49 to -0.69; P < .001) and vs olopatadine (P = .03) and mometasone (P = .02). Similar significant improvements in iTNSS were also observed with GSP301 (P < .05 for all). Furthermore, GSP301 significantly improved overall ocular symptoms, individual nasal and ocular symptoms, and quality of life vs placebo (P ≤ .001 for all). Onset of action for GSP301 was observed within 15 minutes and was maintained at all subsequent timepoints. Treatment-emergent AEs occurred in 15.6%, 12.6%, 9.6%, and 9.5% of patients in the GSP301, olopatadine, mometasone, and placebo groups, respectively. CONCLUSION: GSP301 is efficacious and well tolerated vs placebo for treating SAR-associated nasal and ocular symptoms, with a rapid onset of action of 15 minutes in adult and adolescent patients 12 years and older. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT02870205.

Abstract licence: CC BY-NC-ND

Abstract Introduction Pharmacotherapy is the main pillar in the treatment of allergic rhinitis. While antihistamines (AH) and intranasal glucocorticosteroids (INCS) have long been part of the therapeutic standard, a pharmacological combination of both active substances in a nasal spray has so far only been implemented and made available in two preparations in Germany. Recently, an intranasal olopatadine hydrochloride-mometasone furoate (Olo-Mom) combination was introduced as a nasal spray for the treatment of seasonal and perennial allergic rhinitis. Methods In a literature search, treatment options for allergic rhinitis were analyzed and the available evidence was determined by searching Medline, PubMed, and the national and international study (ClinicalTrials.gov) and guideline registers and the Cochrane Library. Human studies published on the topic in the period up to and including August 2023 were taken into account. Results Based on the international literature and previous experience, the results are summarized and recommendations are given. The drugs used in the pharmacotherapy of AR primarily include INCS, intranasal and oral AH, leukotriene antagonists, intranasal cromoglicic acid preparations, intranasal and oral vasoconstrictors, and nasal rinses. For patients with intermittent and persistent allergic rhinitis, INCS are the first-line therapy, but in many patients they do not work sufficiently or quickly enough. The fixed combination Olo-Mom nasal spray showed significant improvements in the Reflective Total Nasal Symptom Score (rTNSS) in two phase II clinical trials with twice-daily and once-daily administration. In phase III studies, Olo-Mom nasal spray administered twice daily showed significant improvements in rTNSS compared to placebo, olopatadine monotherapy, and mometasone monotherapy. Conclusion In summary, AH and INCS will remain the main groups of active ingredients in the treatment of allergic rhinitis in the future. In combination preparations such as the new combination nasal spray olopatadine hydrochloride-mometasone furoate, they are highly effective and safe, thus opening up new perspectives, especially for patients with moderate and severe allergic rhinitis from the age of 12 years.

Abstract licence: CC BY

The deposition, residence time, and dissolution profile of nasal suspensions containing corticosteroids play a key role in their in vivo efficacy after administration. However, the conventional methods available to characterize nasal products appear to be unsuitable to exhaustively cover these aspects. The work aims to investigate technological aspects of Ryaltris (mometasone furoate and olopatadine hydrochloride nasal spray) compared to other commercial anti-allergic nasal products, namely, Dymista (azelastine hydrochloride and fluticasone propionate), Nasonex (mometasone furoate), and Avamys (fluticasone furoate). Innovative characterization methods were combined with more traditional approaches to investigate the anti-allergic nasal sprays. These methods applied together allowed to differentiate between the different products and provided a clear picture of the nasal product behavior in terms of drug dissolution and deposition. In particular, the dissolution tests were performed exploiting the Respicell® apparatus, an innovative technique that allows for the investigation of inhalation products. Then, formulation viscosities were considered along with a formulation flow test on an inclined plane. Finally, the intranasal deposition profile of the commercial formulations was determined using a silicon nasal cast. The results highlight in vitro significant differences in terms of viscosity as well as dissolution rate of the nasal products, with Ryaltris showing a higher viscosity and lower flow compared to other products, which, along with a corticosteroid faster dissolution rate than Dymista, suggest a potential advantage in terms of clinical behavior.

Abstract licence: CC BY