Allergic rhinitis is a common condition with increasing prevalence and is associated with several comorbid disorders such as bronchial asthma and atopic dermatitis. If allergen avoidance is not possible, allergen-specific immunotherapy is the only causal treatment option. Areas covered: This review focuses on current treatments and the future outlook for allergic rhinitis. Pharmacotherapy includes mast cell stabilizers, antihistamines, glucocorticosteroids (GCSs), leukotriene receptor antagonists, and nasal decongestants. Nasal GCSs are currently regarded as the most effective treatment and are considered first-line therapy together with non-sedating antihistamines. The new formulation MP29-02 combines the nasal GCS fluticasone propionate with azelastine in one single spray and has achieved greater improvements than those under monotherapy with modern GCSs or antihistamines. Furthermore, this review discusses allergen immunotherapy alone and in combination with modern monoclonal antibodies. Expert opinion: Despite the variety of medications for allergic rhinitis, ranging from general symptomatic agents like GCSs or decongestants, to more specific ones like histamine receptor or leukotriene blockers, to causal therapy like immunotherapy, many patients still experience treatment failures or unsatisfactory results. The ultimate goal may be to endotype every downstream pathway separately in order to offer patients individualized, targeted therapy with specific antibodies against the respective pathway.

Nasal cavity breakthrough to the airways of the lungs is associated with nasally inhaled droplets whose size is smaller than ca. 10 μm aerodynamic diameter that behave as an aerosol rather than a spray in terms of their transport. The purpose of the present laboratory-based study was to evaluate a nasal product quality control procedure involving a new inlet for the quantification of mass of such droplets emitted by commercially available aqueous nasal spray pump products by cascade impactor. This inlet is more representative of the adult nasal vestibule in terms of entry angle for the spray as well as internal volume for plume expansion. Sampling was also undertaken via a spherical 1-L glass expansion vessel as inlet, previously established for quantification of these aerosol droplets. The selected solution- and suspension-formulated products containing azelastine and fluticasone propionate respectively were shown to contain < 1% of the total spray mass per actuation associated with droplets < 14.1 μm aerodynamic diameter. These measurements were consistent with laser diffraction-based measurements of the entire droplet size distribution. Comparable measures of aerosol droplet mass fraction were obtained when the spray was sampled by the cascade impactor method using either the 1-L glass expansion chamber or the new metal inlet as entry for the spray produced by either product evaluated. We conclude that the metal inlet has the potential to be adopted as a suitable induction port in the assessment of nasal product quality, where currently no standardized inlet exists.

Background: Green solvents such as microemulsion were used in the proposed method because they play a vital role in the analytical method's influence on the environment. Objective: A highly sensitive, specific, and validated stability-indicating eco-friendly green microemulsion liquid chromatography (MELC) method was developed for separation of the antihistaminic drug Azelastine HCl (AZL) from its degradation products with application to degradation kinetics. Methods: Chromatographic separation was operated on a C18 column with a microemulsion mobile phase, which consists of 0.1 M sodium dodecyl sulphate, 10% n-propanol, 1% n-octanol, and 0.3% triethylamine, by using 0.02 M phosphoric acid at pH 3.5 and irbesartan as internal standard. The eluted compounds were monitored at 210 nm with flow rate 1 mL/min at ambient temperature. Results: A linear dependence of the peak area on drug concentration over the concentration range of 0.1 to 25 μg/mL was achieved with an LOD of 0.04 μg/mL and an LOQ of 0.10 μg/mL. Moreover, the proposed method was successfully applied for determination of AZL in eye drops and metered dose nasal inhaler as well as to study the kinetics of alkaline, acidic, neutral, oxidative, and photolytic degradation processes of AZL according to the International Council for Harmonization guidelines. Conclusions: The proposed method could be used as a harmless alternative for quality control analysis of the mentioned drug, without interference from dosage form additives or decomposition products. Highlights: A highly sensitive stability-indicating eco-friendly green MELC method was developed for the separation of the antihistaminic drug AZL from its degradation products.

We report herein detailed structural insights into the ligand recognition modes guiding bromodomain selectivity, enrichment analysis and docking-based database screening for the identification of the FDA-approved drugs that have potential to be the human BRD4 inhibitors. Analysis of multiple X-ray structures prevailed that the lysine-recognition sites are highly conserved, and apparently, the dynamic ZA loop guides the specific ligand-recognition. The protein-ligand interaction profiling revealed that both BRD2 and BRD4 shared hydrophobic interaction of bound ligands with PRO-98/PRO-82, PHE-99/PHE-83, LEU-108/LEU-92 and direct H-bonding with ASN-156/ASN-140 (BRD2/BRD4), while on the other hand the water-mediated H-bonding of bound ligands with PRO-82, GLN-85, PRO-86, VAL-87, ASP-88, LEU-92, TYR-97 and MET-132, and aromatic π-π stacking with TRP-81 prevailed as unique interaction in BRD4, and were not observed in BRD2. Subsequently, through ROC curve analysis, the best enrichment was found with PDB-ID 4QZS of BRD4 structures. Finally, through docking-based database screening study, we found that several drugs have better binding affinity than the control candidate lead (+)-JQ1 (Binding affinity = -7.9 kcal/mol), a well-known BRD4 inhibitor. Among the top-ranked drugs, azelastine, a selective histamine H1 receptor antagonist, showed the best binding affinity of -9.3 kcal/mol and showed interactions with several key residues of the acetyl lysine binding pocket. Azelastine may serve as a promising template for further medicinal chemistry. These insights may serve as basis for structure-based drug design, drug repurposing and the discovery of novel BRD4 inhibitors. Communicated by Ramaswamy H. Sarma.

A novel stability-indicating UPLC and CE method was established and validated for the determination of azelastine hydrochloride (AZL) and its genotoxic impurity, benzohydrazide, in the presence of benzalkonium chloride. The developed UPLC method was based on chromatographic separation using a C18 column as a stationary phase and acetonitrile-(0.1% w/v) aqueous sodium lauryl sulfate (55:45, v/v, pH 5 with phosphoric acid) as a mobile phase with a flow rate of 1.2 mL/min and UV detection at 215 nm. The chromatographic run time was ~2 min. The developed CE method depended on using a stationary phase of Standard Bare Fused Silica Capillaries (75 μm i.d. × 59 cm and 50 cm detection length) and the applied voltage was 30 kV using 40 mm phosphate buffer (pH 2 with aqueous H3 PO4 ); the detection wavelength was 225 nm. The analysis time was about 6 min. The suggested methods were successfully applied for the analysis of AZL in a pharmaceutical preparation. The validity of the developed methods was assessed by applying the standard addition technique and no interference from excipients was observed. The results obtained by the proposed methods were statistically analyzed and compared with the manufacturer's method and no significant difference was found between the compared methods.

Small occasional doses of azelastine nasal spray would not be expected to cause any adverse effects in breastfed infants. Larger doses or more prolonged use of the nasal spray may cause drowsiness and other effects in the infant or decrease the milk supply, particularly in combination with a sympathomimetic such as pseudoephedrine or before lactation is well established. Infant rejection of the breast might occur because of the bitter taste of the drug. The oral, nonsedating antihistamines are preferred alternatives. Because absorption from the eye is limited, azelastine would not be expected to cause any adverse effects in breastfed infants. To substantially diminish the amount of drug that reaches the breastmilk after using eye drops, place pressure over the tear duct by the corner of the eye for 1 minute or more, then remove the excess solution with an absorbent tissue.