Efficient UPLC and CE methods for the simultaneous determination of azelastine hydrochloride and its genotoxic impurity.

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.

Azelastine nasal spray in the management of seasonal allergic rhinitis.

Azelastine is a novel, investigational, antiallergy medication that inhibits the generation, release, and/or end-organ activity of multiple mediators of the inflammatory process in vitro and in vivo. Azelastine is capable of inhibiting both early-phase and late-phase allergic responses in animals and humans. In this 2-day trial in patients with seasonal allergic rhinitis, we evaluated the onset of action, duration of effect, and safety and efficacy of azelastine nasal solution (Astelin N.S.) in an outdoor, highly allergenic environment. Two hundred ninety-four patients who satisfied entry criteria were randomized to azelastine 2 sprays/nostril q24h or q12h, oral chlorpheniramine maleate 12 mg q12h, or placebo in this multicenter, double-blind, parallel-group study. Rhinitis symptoms were analyzed individually and combined as total and major symptom complexes. For both azelastine treatment groups, the overall mean percent improvements in the total and major symptom complex severity scores were statistically significant (P < or = .05) versus placebo. Improvements in rhinitis symptoms were observed by the second hour after administration of azelastine and lasted up to 24 hours. The therapeutic effect of azelastine was apparent for all rhinitis symptoms, not just one or a few symptoms. Seventy-three percent of the patients treated with azelastine reported overall improvement upon global assessment of their symptoms. Adverse effects with azelastine were generally mild or moderate. Azelastine nasal spray, administered either once or twice daily, was effective in treating the symptoms of seasonal allergic rhinitis and demonstrated a rapid onset of action with a duration of response lasting 12 to 24 hours.

Double-blind assessment of azelastine in the treatment of perennial allergic rhinitis.

Azelastine is a chemically novel multifunctional antiallergy investigational drug capable of inhibiting mast-cell activation and the synthesis and/or release of chemical mediators of the upper and lower airway inflammatory response. In previous controlled clinical trials, azelastine was shown to be effective in treating the symptoms of both seasonal allergic rhinitis and perennial allergic rhinitis. The objective of this 8-week double-blind trial was to evaluate further azelastine's efficacy and safety in improving the symptoms of perennial allergic rhinitis over a prolonged period of treatment. One hundred ninety-nine patients with symptomatic perennial allergic rhinitis were randomized to receive in a double-blind fashion azelastine, 2 mg bid, clemastine fumarate, 1.34 mg bid, or placebo bid for 8 weeks. Patients treated with azelastine had superior mean percent improvements in the total symptom complex score (nose blows, sneezes, stuffy nose, runny nose, itchy nose, and itchy eyes/ears/throat) versus placebo at each evaluation point and overall across all 8 weeks (P < .01) of the trial. Improvements in the individual symptoms of rhinitis were statistically significant (P < or = .04) for nose blows, sneezes, runny nose, itchy nose, and itchy eyes, ears, and throat. Treatment with azelastine also resulted in a clinically meaningful improvement in nasal congestion. Improvement in congestion was accompanied by a decreased requirement for backup decongestant medication. The adverse experiences were generally mild and well tolerated. Azelastine provided effective prolonged relief of the symptoms of perennial allergic rhinitis with no adverse effects that would limit its long-term use.

Azelastine nasal spray as adjunctive therapy to azelastine tablets in the management of seasonal allergic rhinitis.

BACKGROUND: Azelastine rhinitis medications (nasal spray and tablets) have been shown to relieve the symptoms of allergic rhinitis. Nevertheless, many rhinitic subjects suffer from acute exacerbations of symptoms that sometimes require additional treatment. OBJECTIVE: To assess the efficacy and safety of azelastine nasal spray as adjunctive therapy to azelastine tablets in the management of symptomatic seasonal allergic rhinitis in subjects who remain symptomatic despite the oral medication. METHODS: A 2-day, randomized, multicenter, double-blind, placebo-controlled, parallel-group study. Two hundred thirty-three subjects with symptomatic allergic rhinitis received azelastine tablets (0.5 mg bid) for a minimum of seven days prior to receiving either azelastine nasal spray (2 sprays per nostril bid) or placebo nasal spray as adjunctive therapy. Efficacy was determined by improvement in rhinitis symptoms that were grouped according to total and major symptom complex severity scores. RESULTS: Mean percent improvements in the total symptom complex severity scores for azelastine were statistically significant (P < or = .05) or showed a trend toward statistical significance (.05 < or = P < .10) versus placebo from the second through the first ten hours after the initial dose and for each of the last five hours of the second day, demonstrating a rapid onset of action and sustained efficacy over the 2-day study period. Azelastine was well tolerated, and no subject discontinued therapy with azelastine due to an adverse experience. CONCLUSION: Azelastine nasal spray can be effectively administered as adjunctive therapy, in an outdoor environment in which subjects are exposed to pollen and other aeroallergens.