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 - 165 . (canceled) 
     
     
         166 . A liquid formulation composition, comprising
 water as a solvent;   poloxamer;   D-panthenol;   methyl paraben; and   a phospholipid as a surfactant dispersed or dissolved in water,   wherein the liquid formulation composition is an emulsion of liquid droplets having volume average particle sizes in the range from about 1 μm to about 100 μm and is characterized by   the phospholipid is present in an amount of about 0.0001 wt % to about 25.0 wt %,   poloxamer is present in an amount of about 0.01 wt % to about 5.0 wt %;   methyl paraben is present in an amount of about 0.001 wt % to about 2.0 wt %;   a surface tension of less than 30 mN/m, and   a pH value from 6.0 to 7.4.   
     
     
         167 . The liquid formulation composition of  claim 166 , further comprising one of ethanol, glycerol, medical silicone oil and edible vegetable oil, or a combination thereof. 
     
     
         168 . The liquid formulation composition of  claim 167 , wherein the phospholipid is a natural phospholipid. 
     
     
         169 . The liquid formulation composition of  claim 168 , further comprising xylitol. 
     
     
         170 . The liquid formulation composition of  claim 169 , further comprising one of bacteriostatic agent, flavoring agent, stabilizer, antioxidant, or a combination thereof. 
     
     
         171 . The liquid formulation composition of  claim 170 , wherein
 the bacteriostatic agent comprises one of parabens or its salts, benzoic acid or its salts, benzyl alcohol, phenylethanol, phenylacetic acid, phenoxyethanol, lauric acid monoglyceride, chlorobutanol, sorbic acid or its salts, calcium propionate, sodium propionate, dehydroacetic acid or its salts, sodium diacetate, benzalkonium chloride, benzalkonium bromide, cetrimide, chlorhexidine acetate, propanediol, carbon dioxide, nisin, natamycin, momordicin, thimerosal, mercuric nitrate, or a combination thereof;   the flavoring agent comprises one of menthol, borneol, lemon oil, patchouli oil, cinnamon oil, jujube tincture, vanillin, peppermint oil, rose oil, eucalyptus oil, spearmint oil, eugenol, citral, jasmine extract, chrysanthemum extract, osmanthus extract, benzyl alcohol, phenylethanol, terpineol, methyl cyclopentenolone, α-amyl cinnamic aldehyde, butyric acid, hexanoic acid, isoamyl acetate, benzyl acetate, linalyl acetate, ethyl propionate, ethyl butyrate, isoamyl butyrate, benzyl butyrate, isoamyl isovalerate, ethyl hexanoate, ethyl heptanoate, ethyl lactate, allyl hexanoate, γ-nonalactone, ethyl maltol, allyl cyclohexyl propionate, maltol, γ-undecalactone, raspberry ketone, benzyl propionate, butyl butyrate, ethyl isovalerate, ethyl formate, benzyl benzoate, methyl pyrazine, 2,3-dimethyl pyrazine, trimethyl pyrazine, 2-acetyl pyrazine, 4-methyl-5-(β-hydroxyethyl) thiazole, 2-acetyl thiazole, 2,3,5,6-tetramethyl pyrazine, hexadecanal, ethyl vanillin, hydroxyl citronellal, or a combination thereof;   the stabilizer comprises one of lecithin, poloxamer, saponin, tannin, glycerin fatty acid ester, sucrose fatty acid ester, propanediol fatty acid ester, cholesterol, cholesterol ester, polyethylene glycol, cellulose or its derivatives, dextrin, Arabic gum, tragacanth gum, pectin cellulose cheese, gelatin, alginic acid, or a combination thereof; and   the antioxidant comprises one of tert-butyl hydroxy anisole, butylated hydroxytoluene, tert-butyl hydroquinone, propyl gallate, ascorbyl palmitate, dilauryl thiodipropionate, 4-hexyl resorcinol, tocopherol, L-ascorbic acid, D-sodium erythorbate, tea polyphenols, rosemary extract, ginger extract, sugar alcohols, amino acids, or a combination thereof.   
     
     
         172 . The liquid formulation composition of  claim 171 , wherein
 the content of the bacteriostatic agent is in the range from 0.001 wt % to 2.0 wt %,   the content of the flavoring agent is in the range from 0.01 wt % to 5.0 wt %, and   the content of the antioxidant is in the range from 0.001 wt % to 5.0 wt %.   
     
     
         173 . The liquid formulation composition of  claim 170 , comprising borneol, glycerin, butanediol, polyethylene glycol, propanediol, hexanediol or sorbitol, or a combination thereof. 
     
     
         174 . The liquid formulation composition of  claim 170 , characterized by an absolute value of zeta potential of greater than 15 mV for the liquid particles. 
     
     
         175 . A medicament delivery device, comprising
 a containment vessel for holding a liquid comprising an outlet; and   held in the containment vessel a liquid formulation composition of  claim 166 .   
     
     
         176 . The medicament delivery device of  claim 175 , wherein the containment vessel is configured to function as a sprayer, allowing controlled spraying of the liquid formulation composition out of the outlet. 
     
     
         177 . The medicament delivery device of  claim 175 , wherein the containment vessel is configured to function as a dropping device, allowing controlled dropping of the liquid formulation composition out of the outlet.