Method and composition for treating rhinitis

Abstract

A pharmaceutical composition for the treatment of rhinitis by nasal or ocular administration comprises zwitterionic cetirizine, polar lipid liposome, a pharmaceutical acceptable aqueous carrier and, optionally, a pharmaceutically acceptable buffer capable of providing a pH of from pH 4.0 to pH 8.0, with the proviso that, if the polar lipid comprises phospholipid, the amount of phospholipid in the composition from is from 10 mg per mL to 120 mg per mL. Also disclosed are methods for its preparation and methods for treating rhinitis by its nasal or ocular administration.

1 . Pharmaceutical composition for the treatment of rhinitis by nasal or ocular administration comprising zwitterionic cetirizine, polar lipid liposome, a pharmaceutical acceptable aqueous carrier and, optionally, a pharmaceutically acceptable buffer capable of providing a pH of from pH 4.0 to pH 8.0, with the proviso that, if the polar lipid comprises phospholipid, the amount of phospholipid in the composition is from 10 mg per mL to 120 mg per mL.  
   
   
       2 . The composition of  claim 1 , wherein the amount of phospholipid is from 17 mg per mL to 120 mg per mL.  
   
   
       3 . The composition of  claim 1 , wherein the amount of phospholipid is from 35 mg per mL to 70 mg per mL.  
   
   
       4 . The composition of  claim 1 , wherein said pH is from 5.0 to 7.0.  
   
   
       5 . The composition of  claim 1 , wherein the zwitterionic cetirizine has been obtained from a chloride or nitrate salt of cetirizine.  
   
   
       6 . The composition of  claim 5 , wherein the salt is cetirizine dinitrate.  
   
   
       7 . The composition of  claim 1 , wherein the buffer is selected from phosphate buffer, citrate buffer, acetate buffer.  
   
   
       8 . The composition of  claim 1  comprising cetirizine or a salt of cetirizine in an amount of from 1 mg/mL to 23 mg/mL calculated on the zwitterionic form.  
   
   
       9 . The composition of  claim 1 , comprising cetirizine or a salt of cetirizine in an amount of from 5.5 mg/mL to 22 mg/mL.  
   
   
       10 . The composition of  claim 1  wherein the liposome is based on a phospholipid or on a mixture of phospholipids.  
   
   
       11 . The composition of  claim 10 , wherein the phospholipid is selected from the group consisting of phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol, phosphatidic acid, and phosphatidylserine  
   
   
       12 . The composition of  claim 10 , wherein at least one phospholipid is of natural origin.  
   
   
       13 . The composition of  claim 10 , wherein at least one phospholipid is of synthetic or semi-synthetic origin.  
   
   
       14 . The composition of  claim 1 , wherein the liposome is based on a glycolipid or a mixture of glycolipids.  
   
   
       15 . The composition of  claim 1 , wherein the liposome consists of a glycolipid or a mixture of glycolipids.  
   
   
       16 . The composition of  claim 14 , where the glycolipid is glycoglycerolipid.  
   
   
       17 . The composition of  claim 16 , wherein the glycoglycerolipid comprises galactoglycerolipid.  
   
   
       18 . The composition of  claim 16 , wherein glycoglycerolipid comprises digalactosyldiacylglycerol.  
   
   
       19 . The composition of  claim 18 , wherein glycoglycerolipid substantially consists of digalactosyldiacylglycerol.  
   
   
       20 . The composition of  claim 14 , wherein the glycolipid is a glycosphingolipid.  
   
   
       21 . The composition of  claim 14 , wherein the glycolipid is a glycophosphatidylinositol.  
   
   
       22 . The composition of  claim 1  comprising at least one antioxidant, chelating agent, preservative, or viscosity-increasing agent.  
   
   
       23 . A process for preparing a pharmaceutical composition for the treatment of rhinitis by nasal or ocular administration comprising zwitterionic cetirizine, polar lipid liposome, a pharmaceutical acceptable aqueous carrier and, optionally, a pharmaceutically acceptable buffer capable of providing a pH of from about pH 4 to about pH 8, with the proviso that, if the polar lipid comprises phospholipid, the amount of phospholipid in the composition is from 10 to 120 mg per mL, comprising 
 (a) providing a polar lipid or a mixture of polar lipids that is swellable in aqueous media;    (b) providing an aqueous solution of cetirizine and buffer having a pH of from pH 4 to pH 8;    (c) adding the polar lipid to the aqueous solution while stirring, thereby forming a cetirizine liposome preparation;    (d) optionally adjusting the pH of the preparation to a desired value within the range of from pH 4 to pH 8 by adding an acid or a base;    (e) optionally adding water or saline or a buffer having a pH of from pH 4 to pH 8 to the preparation to obtain a desired final batch volume;    (f) homogenising the preparation to obtain said pharmaceutical composition.    
   
   
       24 . The process of  claim 23 , wherein the amount of phospholipid in the composition is from 17 to 120 mg per mL.  
   
   
       25 . The process of  claim 23 , wherein the amount of phosphlipid in the composition is from 35 mg to 70 mg per mL.  
   
   
       26 . The process of  claim 23 , wherein the pH is from from pH 5.0 to pH 7.0.  
   
   
       27 . The process of  claim 23 , wherein said mixture of swellable polar lipids has be pre-treated with organic solvent.  
   
   
       28 . The process of  claim 23 , wherein homogenisation comprises at least one of vigorous mechanical mixing, shaking, vortexing, or rolling.  
   
   
       29 . The process of  claim 22 , additional comprising reduction of liposome size.  
   
   
       30 . The process of  claim 29 , wherein the reduction of liposome size comprises extrusion through a membrane filter or high-pressure homogenization or both.  
   
   
       31 . A method for the manufacture of a pharmaceutical composition for the treatment of rhinitis comprising combining cetirizine and a pharmacologically acceptable liposomal carrier comprising polar lipid dispersed in an aqueous medium, with the proviso that, if the polar lipid comprises phospholipid, the amount of phospholipid in the composition is from 10 mg to 120 mg per mL.  
   
   
       32 . The method of  claim 31 , wherein the polar lipid is glycoglycerolipid.  
   
   
       33 . The method of  claim 32 , wherein the glycoglycerolipid comprises galactoglycerolipid.  
   
   
       34 . A method of treating rhinitis comprising nasal administration of a pharmacologically effective amount of the composition of  claim 1 .  
   
   
       35 . A method of treating rhinitis comprising ocular administration of a pharmacologically effective amount of the composition  claim 1.