Nasal pharmaceutical formulations and methods of using the same

Abstract

Nasal pharmaceutical formulations comprising a drug substance having a specific particle size distribution profile are disclosed herein. Such profile provides increased bioavailability, increased efficacy or prolonged therapeutic effect of the drug substance when administered intranasally. The formulations of the present invention may comprise one or more corticosteroids having a specific particle size distribution profile. In a preferred embodiment, the corticosteroid is beclomethasone or a pharmaceutically acceptable derivative thereof for the treatment of one or more symptoms of rhinitis. Preferably, the drug substance is beclomethasone dipropionate. The formulations herein may be provided as an aqueous suspension suitable for inhalation via the intranasal route.

1 . A nasal formulation comprising a microcrystalline suspension of fluticasone suspended in an aqueous medium, about 0.001% to about 5% w/w of a humectant, and about 0.05 mg/ml to about 0.5 mg/ml of a complexing agent; wherein the suspended fluticasone comprises about 50 mcg and has the following particle size distribution profile: 
 (i) about 10% of the fluticasone particles have a particle size of less than 0.4 microns;    (ii) about 25% of the fluticasone particles have a particle size of less than 0.8 microns;    (iii) about 50% of the fluticasone particles have a particle size of less than 1.5 microns;    (iv) about 75% of the fluticasone particles have a particle size of less than 2.9 microns; and    (v) about 90% of the fluticasone particles have a particle size of less than 5.2 microns;    wherein the formulation is suitable for administration to an individual's nasal mucosa.    
     
     
         2 . A method of treating one or more symptoms of rhinitis comprising the steps of applying to an individual's nasal mucosa a microcrystalline suspension of fluticasone suspended in an aqueous medium, about 0.001% to about 5% w/w of a humectant, and about 0.05 mg/ml to about 0.5 mg/ml of a complexing agent; wherein no more than about 10% of the suspended microcrystalline fluticasone particles have a particle size less than about 0.4 microns and about 100% of the suspended microcrystalline fluticasone particles have a particle size less than about 5.3 microns.  
     
     
         3 . A method of reducing the amount of fluticasone necessary for the treatment of one or more symptoms of rhinitis comprising administering only 1 inhalation of a microcrystalline suspension of fluticasone in each nostril of an individual per day; wherein the suspended fluticasone comprises about 50 mcg and has the following particle size distribution profile: 
 (i) about 10% of the fluticasone particles have a particle size of less than 0.5 microns;    (ii) about 25% of the fluticasone particles have a particle size of less than 1.0 microns;    (iii) about 50% of the fluticasone particles have a particle size of less than 1.5 microns;    (iv) about 75% of the fluticasone particles have a particle size of less than 2.5 microns; and    (v) about 90% of the fluticasone particles have a particle size of less than 4.0 microns.