Self-preserved antibacterial nasal, inhalable, and topical ophthalmic preparations and medications

Abstract

Self-preserved nasal, inhalable and topical ophthalmic preparations and medications which destroy, inhibit or therapeutically significantly limit microbial growth within said preparations or medications. The nasal, inhalable, and topical ophthalmic preparations and medications are mildly buffered and maintain a stable pH at pH 3.5 or lower.

What is claimed:  
     
         1 . A self-preserved preservative-free topical ophthalmic, inhalable or nasal formulation comprising: 
 a pharmaceutically acceptable excipient or additive selected from the group consisting of a pharmaceutically acceptable excipient or additive selected from the group consisting of dextrose, polyethylene glycol (PEG), hydroxypropyl methylcellulose (HPMC), sodium chloride, potassium chloride, calcium chloride, magnesium chloride, phosphoric acid, disodium edetate, bicarbonate, phosphate, povidone, carboxymethylcellulose, hydroxyethylcellulose, methylcellulose, microcrystalline cellulose, other cellulose derivatives, glycerin, polyvinyl alcohol, dextran 40, dextran 70, mannitol, gelatin, polyols, polysorbate 80, propylene glycol, zinc sulfate, poloxamer 188, 282, 407, ephedrine hydrochloride, naphazoline hydrochloride, oxymetazoline hydrochloride, phenylephrine hydrochloride, tetrahydrozoline hydrochloride, xylometazoline hydrochloride, lecithin, oleic acid and sorbitan, pheniramine maleate, pyrilamine maleate, antazoline phosphate, glycine, camphor, eucalyptol, menthol, benzyl alcohol, lavender oil, tyloxapol, bornyl acetate, and phenylethyl alcohol, alone or in admixture; and    a buffering agent;    said formulation adjusted to pH from about pH 1.5 to pH about 3.5.    
     
     
         2 . The formulation of  claim 1  wherein pH is adjusted to pH from about pH 2.0 to about 2.5.  
     
     
         3 . The formulation of  claim 2  wherein the pH is about 2.5.  
     
     
         4 . The formulation of  claim 3  wherein the buffering agent is acetic, citric, formic, glutaric, glycolic, lactic, maleic or tartaric acid or a salt thereof.  
     
     
         5 . The formulation of  claim 4  wherein the buffering agent is citric acid.  
     
     
         6 . The formulation of  claim 5  wherein the excipient, additive or a pharmaceutical agent is present in amount from 0.001 to about 8% and wherein the buffering agent is present in amount from about 0.001 to about 0.02%.  
     
     
         7 . The formulation of  claim 6  comprising about 1-8% of polyethylene glycol, about 0.1% to about 0.3% of hydroxypropyl methylcellulose, about 0.01% to about 0.02% citric acid and purified water, wherein the pH is adjusted to about pH 2.5.  
     
     
         8 . The formulation of  claim 7  comprising about 8% of polyethylene glycol, about 0.3% of hydroxypropyl methylcellulose, about 0.01% citric acid and purified water, wherein the pH is adjusted to about pH 2.5.  
     
     
         9 . The formulation of  claim 8  wherein the pH is adjusted with an acid or a base.  
     
     
         10 . The formulation of  claim 9  wherein the acid is hydrochloric acid or sulphuric acid and wherein the base is sodium hydroxide or ammonium hydroxide.  
     
     
         11 . The formulation of  claim 7  additionally comprising about 2 to 6% of dextrose.  
     
     
         12 . The formulation of  claim 11  comprising about 4% of dextrose, about 1% of polyethylene glycol, about 0.3% of hydroxypropyl methylcellulose and about 0.01% of citric acid.  
     
     
         13 . The formulation of  claim 12  wherein the pH is adjusted with an acid or a base.  
     
     
         14 . The formulation of  claim 9  wherein the acid is hydrochloric acid, phosphoric acid or sulphuric acid and wherein the base is sodium hydroxide or ammonium hydroxide.  
     
     
         15 . A method for preparation of a topical ophthalmic, nasal or inhalable self-preserved solution comprising steps of: 
 a) preparing a formulation comprising 
 a pharmaceutically acceptable excipient or additive selected from the group consisting of dextrose, polyethylene glycol (PEG), hydroxypropyl methylcellulose (HPMC), sodium chloride, potassium chloride, calcium chloride, magnesium chloride, phosphoric acid, disodium edetate, bicarbonate, phosphate, povidone, carboxymethylcellulose, hydroxyethylcellulose, methylcellulose, microcrystalline cellulose, other cellulose derivatives, glycerin, polyvinyl alcohol, dextran 40, dextran 70, mannitol, gelatin, polyols, polysorbate 80, propylene glycol, zinc sulfate, poloxamer 188, 282, 407, ephedrine hydrochloride, naphazoline hydrochloride, oxymetazoline hydrochloride, phenylephrine hydrochloride, tetrahydrozoline hydrochloride, xylometazoline hydrochloride, lecithin, oleic acid and sorbitan, pheniramine maleate, pyrilamine maleate, antazoline phosphate, glycine, camphor, eucalyptol, menthol, benzyl alcohol, lavender oil, tyloxapol, bornyl acetate, and phenylethyl alcohol, alone or in admixture; and  
 a buffering agent; and  
   b) adjusting pH of said formulation to from about pH 1.5 to pH about 3.5.    
     
     
         16 . The method of  claim 15 , wherein the buffering agent is citric acid or sodium citrate and wherein the pH is adjusted to pH about 2.0 to about 2.5.  
     
     
         17 . The method of  claim 16 , wherein the pH is adjusted to pH about 2.5.  
     
     
         18 . The method of  claim 17 , wherein the solution is used as a topical eye preparation for administration of a pharmaceutical agent, artificial tear, contact lens solution or eye irrigating solution.  
     
     
         19 . The method of  claim 18 , the pharmaceutical agent is selected from the group consisting of an analgesic, anti-inflammatory, astringent, antihistamine, mast cell stabilizer, diagnostic aid, fluorescein, miotic, mydriatic, antibiotic, antiviral, antifungal, vasoconstricting agent, antiglaucoma medication, hypertonicity agent, decongestant, bronchodilator and topical anesthetic, said pharmaceutical agent present in from about 0.001 to about 8%.  
     
     
         20 . The method of  claim 19  wherein the anesthetic is proparacaine, tetracaine, lidocaine, benoxinate, and bupivicaine.