Liquid formulation compositions, medicament delivery devices, and methods of preparation and use thereof

Abstract

The invention provides liquid formulation compositions and medicament delivery devices, and methods for preparing and using the same. For example, the liquid formulation composition is an emulsion including a solvent and liquid particles, which includes surfactants and are dispersed in the solvent. The volume average particle size of the liquid particles is less than about 100 μm; the surface tension of the liquid formulation composition is less than about 60 mN/m; and the absolute value of zeta potential is greater than about 15 mV. The containment vessel may be a sprayer or a dropping device. The invention also provides methods for preparation of the liquid formulation compositions and medicament delivery devices as well as methods for using the same in treatment of various diseases and condition, for example, otitis media, otitis externa, rhinitis, sinusitis, lower respiratory tract inflammation, xerostomia (dry mouth), xerophthalmia (dry eyes) and xeromycteria (dry nose).

What is claimed is: 
     
         1 . A liquid formulation composition, comprising
 a solvent; and   a surfactant dispersed or dissolved in the solvent,   
       wherein the liquid formulation composition is characterized by
 a surface tension of less than about 60 mN/m, and 
 a pH value from about 5.0 to about 7.4. 
 
     
     
         2 . The liquid formulation composition of  claim 1 , wherein the solvent comprises one of water, ethanol, glycerol, medical silicone oil and edible vegetable oil, or a combination thereof. 
     
     
         3 . The liquid formulation composition of  claim 1 , wherein the surface tension of the liquid formulation composition is less than about 40 mN/m. 
     
     
         4 . (canceled) 
     
     
         5 . The liquid formulation composition of  claim 1 , wherein the pH value of the liquid formulation composition is from about 6.0 to about 7.4. 
     
     
         6 . The liquid formulation composition of  claim 1 , wherein the surfactant is a natural surfactant or a synthetic surfactant, or a combination thereof. 
     
     
         7 . The liquid formulation composition of  claim 6 , wherein the surfactant comprises one of natural phospholipid, sterol, pulmonary surfactant, stearic acid, oleic acid, lauric acid, benzalkonium chloride, benzalkonium bromide, cetrimide, sorbitan fatty acid, polysorbate, polyoxyethylene stearate, polyoxyethylene-fatty alcohol ether, poloxamer, dipalmitoyl phosphatidylcholine, cholesterol, cholesteryl ester, phosphatidyl ethanolamine, phosphatidylglycerol, phosphatidylserine, polyethylene glycol, or a combination thereof. 
     
     
         8 . The liquid formulation composition of  claim 6 , wherein the surfactant comprises one of lecithin, sterol, pulmonary surfactant, poloxamer, dipalmitoyl phosphatidylcholine, cholesterol, cholesteryl ester, phosphatidyl ethanolamine, phosphatidylglycerol, phosphatidylserine, polyethylene glycol, or a combination thereof. 
     
     
         9 . The liquid formulation composition of  claim 1 , wherein
 the content of the surfactant is in the range from about 0.0001 wt % to about 25.0 wt %, and   the content of the solvent is in the range from about 75.0 wt % to about 99.9999 wt %.   
     
     
         10 . The liquid formulation composition of  claim 1 , further comprising an active pharmaceutical ingredient, wherein the active pharmaceutical ingredient is selected from one of medicines for treating rhinitis, sinusitis, lower respiratory tract inflammation, otitis media, otitis externa, xerostomia, xerophthalmia, xeromycteria, or a combination thereof. 
     
     
         11 . The liquid formulation composition of  claim 10 , wherein the active pharmaceutical ingredient comprises one of cortisone, hydrocortisone, beclomethasone, triamcinolone acetonide, mometasone, dexamethasone, fluocinolone acetonide, budesonide, fluticasone, ephedrine hydrochloride, xylometazoline hydrochloride, levocabastine hydrochloride, azelastine hydrochloride, fructus  xanthii , dandelion, radix scutellariae, bitter gourd, herba ephedrae, flos  magnoliae , herba asari, radix angelicae dahuricae, rhizome acori tatarinowii,  catechu , Longjing tea, cortex phellodendri, ofloxacin, levofloxacin, norfloxacin, lomefloxacin, tosufloxacin, sparfloxacin, roxithromycin, chloromycetin, penicillin, clindamycin, nitrofurazone, amoxicillin, ampicillin, clavulanate potassium, cefaclor, cefixime, cefdinir, cephradine, cephalexin, cefpodoxime, cefuroxime axetil, cefprozil, azithromycin, minocycline, acetyl midecamycin, acetylspiramycin, metronidazole, musk, potassium aluminium sulfate anhydrous, calamine, borneol, cochineal, cacumen platycladi,  echinacea  root, baptisia  tinctoria  root, D-panthenol, glycerin, hyaluronic acid, butanediol, polyethylene glycol, propanediol, hexanediol, xylitol, sorbitol, or a combination thereof. 
     
     
         12 . The liquid formulation composition of  claim 11 , wherein
 the content of the surfactant is in the range from about 0.0001 wt % to about 25.0 wt %,   the content of the solvent is in the range from about 70.0 wt % to about 99.9989 wt %, and   the content of the active pharmaceutical ingredient is in the range from about 0.001 wt % to about 5.0 wt %.   
     
     
         13 . The liquid formulation composition of  claim 1 , further comprising one of bacteriostatic agent, flavoring agent, stabilizer, antioxidant, or a combination thereof. 
     
     
         14 - 16 . (canceled) 
     
     
         17 . A liquid formulation composition, comprising
 a solvent; and   liquid particles dispersed in the solvent, the liquid particles comprising a surfactant,   
       wherein
 the liquid formulation composition is an emulsion; 
 the volume average particle size of the liquid particles is less than about 100 μm; and 
 the liquid formulation composition is characterized by a surface tension of less than about 60 mN/m and an absolute value of zeta potential of greater than about 15 mV. 
 
     
     
         18 . The liquid formulation composition of  claim 17 , wherein the solvent is one of water, ethanol, glycerol, medical silicone oil and edible vegetable oil, or a combination thereof. 
     
     
         19 . The liquid formulation composition of  claim 17 , wherein the absolute value of zeta potential of the liquid formulation composition is greater than about 20 mV. 
     
     
         20 . (canceled) 
     
     
         21 . The liquid formulation composition of  claim 17 , wherein the volume average particle size of the liquid particles is from about 1 μm to about 100 μm. 
     
     
         22 . The liquid formulation composition of  claim 17 , wherein the volume average particle size of the liquid particles is from about 50 nm to about 500 nm. 
     
     
         23 . The liquid formulation composition of  claim 17 , wherein the pH value of the liquid formulation composition is from about 5.0 to about 7.4. 
     
     
         24 . (canceled) 
     
     
         25 . The liquid formulation composition of  claim 17 , wherein the surface tension of the liquid formulation composition is less than about 40 mN/m. 
     
     
         26 . (canceled) 
     
     
         27 . The liquid formulation composition of  claim 17 , wherein the surfactant is a natural surfactant or a synthetic surfactant, or a combination thereof. 
     
     
         28 . The liquid formulation composition of  claim 27 , wherein the surfactant comprises one of natural phospholipid, sterol, pulmonary surfactant, stearic acid, oleic acid, lauric acid, benzalkonium chloride, benzalkonium bromide, cetrimide, sorbitan fatty acid, polysorbate, polyoxyethylene stearate, polyoxyethylene-fatty alcohol ether, poloxamer, dipalmitoyl phosphatidylcholine, cholesterol, cholesteryl ester, phosphatidyl ethanolamine, phosphatidylglycerol, phosphatidylserine, polyethylene glycol, or a combination thereof. 
     
     
         29 . The liquid formulation composition of  claim 27 , wherein the surfactant comprises one of lecithin, sterol, pulmonary surfactant, poloxamer, dipalmitoyl phosphatidylcholine, cholesterol, cholesteryl ester, phosphatidyl ethanolamine, phosphatidylglycerol, phosphatidylserine, polyethylene glycol, or a combination thereof. 
     
     
         30 . The liquid formulation composition of  claim 17 , wherein
 the content of the surfactant is in the range from about 0.1 wt % to about 25.0 wt %, and   the content of the solvent is in the range from about 75.0 wt % to about 99.9 wt %.   
     
     
         31 . The liquid formulation composition of  claim 17 , wherein the liquid formulation composition further comprises one of bacteriostatic agent, flavoring agent, stabilizer, antioxidant, or a combination thereof. 
     
     
         32 . (canceled) 
     
     
         33 . (canceled) 
     
     
         34 . A liquid formulation composition, comprising
 an active pharmaceutical ingredient;   a solvent; and   liquid particles dispersed in the solvent, the liquid particles comprising a surfactant,   
       wherein
 the liquid formulation composition is an emulsion; 
 the volume average particle size of the liquid particles is less than about 100 μm; 
 the active pharmaceutical ingredient is selected from one of medicines for treating rhinitis, sinusitis, lower respiratory tract inflammation, otitis media, otitis externa, xerostomia, xerophthalmia, xeromycteria, or a combination thereof; and 
 the liquid formulation composition is characterized by a surface tension of less than about 60 mN/m and an absolute value of zeta potential of greater than about 15 mV. 
 
     
     
         35 - 51 . (canceled) 
     
     
         52 . A medicament delivery device, comprising
 a containment vessel for holding a liquid comprising an outlet; and   a liquid formulation composition held in the containment vessel,   
       wherein
 the liquid formulation composition is an emulsion or a solution and comprises a solvent and, a surfactant dissolved therein; 
 the liquid formulation composition is characterized by a surface tension of less than about 60 mN/m and a pH value from about 5.0 to about 7.4. 
 
     
     
         53 - 70 . (canceled) 
     
     
         71 . A medicament delivery device, comprising
 a containment vessel for holding a liquid comprising an outlet; and   a liquid formulation composition held in the containment vessel,   
       wherein
 the liquid formulation composition is an emulsion or a solution and comprises a solvent and, dispersed therein, liquid particles comprising a surfactant; 
 the volume average particle size of the liquid particles is less than about 100 μm; and 
 the liquid formulation composition is characterized by a surface tension of less than about 60 mN/m and an absolute value of zeta potential of greater than about 15 mV. 
 
     
     
         72 - 165 . (canceled)