Development and validation of stability indicating method for the determination of exemestane by reverse phase high performance liquid chromatography.

Exemestane is an aromatase inhibitor used in the treatment of breast cancer. A selective stability-indicating reversed-phase high performance liquid chromatography (RP-HPLC) method has been developed which can separate and accurately quantitate low levels of exemestane. The stability-indicating capability of the method was demonstrated by adequate separation of exemestane and all the degradation product peaks from exemestane peak and also from each other in stability samples of exemestane. Chromatographic separation of exemestane and its degraded products were achieved by using isocratic elution at a flow rate of 1.0 mL/min on a C18 reverse phase column (Phenomenex, size: 250 × 4.60 mm, particle size 5 µm) at ambient temperature. The mobile phase used for the analysis was acetonitrile-water (60:40, %v/v) with UV visible detection at 242 nm. The proposed method was used to study the degradation behavior of drug under various stress conditions as per ICH recommended guidelines.

Comparative efficacy and safety of twice daily fluticasone propionate powder versus placebo in the treatment of moderate asthma.

BACKGROUND: Fluticasone propionate, an inhaled corticosteroid with negligible systemic bioavailability via the oral route, is efficacious in the treatment of asthma when administered via metered-dose inhaler. OBJECTIVE: To evaluate the efficacy and safety of inhaled fluticasone propionate powder in patients with moderate asthma previously treated with an inhaled corticosteroid. METHODS: This was a randomized, double-blind, placebo-controlled, parallel-group, multicenter study of 342 adolescent and adult patients with moderate asthma [forced expiratory volume in 1 second (FEV1) between 50% and 80% of predicted] treated previously by beclomethasone dipropionate or triamcinolone acetonide. Patients received fluticasone propionate powder 50 micrograms, 100 micrograms, 250 micrograms, or placebo via a breath-actuated inhalation device, the Diskhaler, twice daily for 12 weeks. RESULTS: Patients in the fluticasone propionate groups experienced a mean increase from baseline to endpoint in FEV1 ranging from 0.43 L to 0.47 L. Patients in the placebo group experienced a mean decrease from baseline of 0.22 L (P < .001). The probability of patients remaining in the study over time without developing signs of exacerbating asthma was significantly greater in the fluticasone propionate groups than in the placebo group (P = .001). Asthma symptom scores, supplemental rescue albuterol use, and number of nighttime awakenings due to asthma requiring treatment also improved significantly with all fluticasone propionate treatment regimens compared with placebo (P < .001). There were no statistically significant differences at endpoint among the three fluticasone propionate groups. No serious drug-related adverse events occurred. CONCLUSIONS: Fluticasone propionate powder (50, 100, and 250 micrograms) was well-tolerated and significantly improved lung function in patients with moderate asthma.

Multicenter trial of fluticasone propionate aqueous nasal spray in ragweed allergic rhinitis.

A 4-week multicenter, double-blind, placebo-controlled, parallel-group trial was carried out with 416 adults with ragweed allergic rhinitis to compare 200 micrograms of fluticasone propionate once daily and 100 micrograms of fluticasone propionate twice daily with placebo. Compared with placebo, both groups receiving fluticasone propionate had greater number of symptom free days (P < .01), lower median symptom scores (P < .01), and greater number of days not requiring rescue medications (P < .001). No significant differences for individual symptoms were found between the two fluticasone propionate groups except that those taking the twice daily dosage used less antihistamine (P < .01) and had greater number of days free of rescue medications (P < .05). Adverse events were comparable between the three groups. These results indicate that topical intranasal fluticasone propionate 200 micrograms once daily and 100 micrograms twice daily are both efficacious and well tolerated.

Dose tolerance study of fluticasone propionate aqueous nasal spray in patients with seasonal allergic rhinitis.

A multicenter, double-blind, parallel-group, dose-tolerance study was conducted to evaluate the safety of fluticasone propionate aqueous nasal spray, a potent new corticosteroid preparation. Ninety-seven adult patients with moderate to severe seasonal allergic rhinitis during the fall weed season received either placebo or fluticasone propionate in doses of 50, 200, or 800 micrograms twice daily for 4 weeks. Safety evaluations included adrenal function evaluation by morning plasma cortisol concentration, response to ACTH stimulation, and 24-hour urinary free cortisol excretion. There was no evidence of effects on adrenal function at any dose. The severity, nature, and frequency of adverse events were similar across all treatment groups, including placebo. Drug-related adverse events were consistent with local nasal irritation. The groups receiving fluticasone propionate showed greater improvement in nasal symptoms (obstruction, rhinorrhea, sneezing, and itching) than did the placebo group. The results demonstrate that fluticasone propionate aqueous nasal spray is safe in doses up to 1600 micrograms per day and effective in the treatment of seasonal allergic rhinitis.