Aqueous-based pharmaceutical composition

Abstract

An aqueous pharmaceutical composition which is capable of being sprayed into the nasal cavity of an individual and which comprises: (A) a pharmaceutically effective amount of solid particles of medicament which is effective in treating a bodily condition by virtue of its being present on the mucosal surfaces of the nasal cavity; and (B) a suspending agent in an amount effective to maintain said particles dispersed uniformly in the composition and to impart to the composition the following thixotropic properties: (i) the viscosity of the position in unsheared form is relatively high, with the composition being in gel-like form; (ii) as the composition is subjected to shear (shaken) in preparation for spraying, the viscosity of the composition becomes relatively low and such that the composition in the form of a mist flows readily into the nasal passages for deposit on the mucosal surfaces of the nasal cavity; and (D) in deposited form on the mucosal surfaces, the viscosity of the composition is relatively high and such that it resists being cleared from the mucosal surfaces by the inherent mucocillary forces which are present in the nasal cavity, a method of use of the composition and a method for preparation of the composition, including in preferred form the use of anti-inflammatory steroid, for example, triamcinoline acetonide, and an odorless form of the composition.

1 . A method for applying solid particles of a medicament to the mucosal surfaces of the nasal cavities comprising spraying a dose of an aqueous pharmaceutical composition containing said medicament into each of the nasal cavities, said dose containing a pharmaceutically effective amount of said medicament, said composition including also a suspending agent in an amount which is effective in maintaining said particles dispersed uniformly in the composition and in imparting to the composition thixotropic properties such that pharmaceutically effective amounts of the medicament are deposited on each of the mucosal surfaces of the anterior regions of the nose, the frontal sinus and the maxillary sinuses and on each of the mucosal surfaces which overlie the turbinates covering the conchas and such that portions of said amounts are retained on each of said mucosal surfaces for at least about an hour. 
     
     
         2 . A method according to  claim 1  wherein the medicament comprises an anti-inflammatory steroid. 
     
     
         3 . A method according to  claim 2  wherein the anti-inflammatory steroid comprises triamcinolone acetonide and said dose includes said triamcinolone acetonide in an amount effective to provide relief from allergic rhinitis symptoms. 
     
     
         4 . A method according to  claim 3  wherein the setting viscosity of the composition is about 50 to about 200 cp and the shear viscosity of the composition is about 400 to about 1000 cp. 
     
     
         5 . A method according to  claim 4  wherein said composition is odorless and includes also a quaternary ammonium compound and a chelating agent and wherein said suspending agent consists essentially of a mixture of microcrystalline cellulose and carboxymethylcellulose sodium. 
     
     
         6 . A method according to  claim 5  wherein said ammonium compound consists essentially of benzalkonium chloride and sid chelating agent consists essentially of EDTA. 
     
     
         7 . A method according to  claim 1  wherein said composition is sprayed by a precompression pump. 
     
     
         8 . An aqueous pharmaceutical composition which is capable of being sprayed into the nasal cavity of an individual and which comprises: (A) a pharmaceutically effective amount of solid particles of medicament which is effective in treating a bodily condition by virtue of its being present on the mucosal surfaces of the nasal cavity; and (B) a suspending agent in an amount effective to maintain said particles dispersed uniformly in the composition and to impart to the composition the following thixotropic properties: (i) the viscosity of the position in unsheared form is relatively high, with the composition being in gel-like form; (ii) as the composition is subjected to shear (shaken) in preparation for spraying, the viscosity of the composition becomes relatively low and such that the composition in the form of a mist flows readily into the nasal passages for deposit on the mucosal surfaces of the nasal cavity; and (D) in deposited form on the mucosal surfaces, the viscosity of the composition is relatively high and such that it resists being cleared from the mucosal surfaces by the inherent mucocillary forces which are present in the nasal cavity. 
     
     
         9 . A composition according to  claim 8  wherein the relatively low viscosity of the composition is about 50 to about 200 cp and the relatively high viscosity of the composition is about 400 to about 1000 cp. 
     
     
         10 . A composition according to  claim 8  wherein the medicament is an anti-inflammatory steroid. 
     
     
         11 . A composition according to  claim 9  wherein the medicament is an anti-inflammatory steroid. 
     
     
         12 . A composition according to  claim 10  wherein the steroid consists essentially of triamcinoline acetonide. 
     
     
         13 . A composition according to  claim 11  wherein the steroid consists essentially of triamcinoline acetonide. 
     
     
         14 . A composition according to  claim 12  which is odorless and which includes a quaternary ammonium compound and a chelating agent. 
     
     
         15 . A composition according to  claim 14  wherein the quaternary ammonium compound consists essentially of benzalkonium chloride, the chelating agent consists essentially of EDTA and the suspending agent consists of a mixture of microcrystalline cellulose and carboxymethyl cellulose sodium. 
     
     
         16 . A composition according to  claim 15  wherein the setting viscosity of the composition is about 400 cp to about 800 cp and the shear viscosity is about 100 cp to about 200 cp. 
     
     
         17 . A method for preparing an aqueous pharmaceutical composition comprising a medicament in the form of solid particles, a dispersing agent for wetting said particles, and a suspending agent for maintaining said particles substantially uniformly dispersed in the composition and for imparting to the composition thixotropic properties comprising: (A) forming an aqueous solution of the dispersing agent and combining the solution with the solid particles to form a suspension of the particles; (B) adding the suspending agent to an aqueous acidic solution to form a thixotropic suspension; and (C) combining each of the suspensions by introducing one of the suspensions into the bottom of the other suspension. 
     
     
         18 . A method according to  claim 17  wherein the suspension of particles is introduced into the bottom of the thixotropic suspension. 
     
     
         19 . A method according to  claim 18  in which the suspension of particles includes particles of triamcinolone acetonide, a hydrophilic non-ionic surfactant and a quaternary ammonium anti-microbial agent and in which the thixotropic suspension includes a chelating agent and an anti-osmotic agent. 
     
     
         20 . A method according to  claim 19  wherein the anti-microbial agent consists essentially of benzalkonium chloride, the chelating agent consists essentially of EDTA and the anti-osmotic agent consists essentially of dextrose.