Compositions and Methods for Making and Using Nanoemulsions

Abstract

The present invention discloses an improved nanoemulsion comprising a uniform and discrete range of very small particle nano-sized diameters. This uniformity results in improved bioavailability of incorporated compounds (i.e., pharmaceuticals or nutraceuticals) as reflected in various pharmacokinetic parameters including, but not limited to, decreased T max , increased C max , and increased AUC. The improved method of making these uniform nanoemulsions utilizes microfluidization which differs in both process and mechanics when compared to conventional milling and grinding techniques used to generate nanoparticulate compositions. Further, the improvement results, in part, from a novel step of mixing a substantially soluble compound into a heated dispersion medium. This is unlike current nanoparticulate composition methods that mix an insoluble compound with an unheated dispersion medium. Further, these nanoemulsions are observed to be bacterial-resistant and stable to extremes in both temperature and pH changes. Consequently, these nanoemulsions are expected to have a significantly prolonged shelf-life than currently available nanoemulsions.

1 . A nanoemulsion comprising a population of particles having diameters between approximately 10 and approximately 110 nanometers, wherein said nanoemulsion is not contaminated by particles having diameters larger than 110 nanometers. 
     
     
         2 . The nanoemulsion of  claim 1 , wherein said particles encapsulate a compound. 
     
     
         3 . The nanoemulsion of  claim 2 , wherein said compound is a pharmaceutical. 
     
     
         4 . The nanoemulsion of  claim 2 , wherein said compound is a nutraceutical. 
     
     
         5 . A nanoemulsion comprising a first and second population of particles, wherein the majority of particles in said first population have diameters between approximately 10 and approximately 20 nanometers, wherein the majority of particles in said second population have diameters between approximately 40 and approximately 80 nanometers, wherein said nanoemulsion is uncontaminated by particles having diameters larger than 110 nanometers. 
     
     
         6 . The nanoemulsion of  claim 5 , wherein said particles encapsulate a compound. 
     
     
         7 . The nanoemulsion of  claim 6 , wherein said compound is a pharmaceutical. 
     
     
         8 . The nanoemulsion of  claim 6 , wherein said compound is a nutraceutical. 
     
     
         9 . A method, comprising:
 a) providing;
 i) a premix comprising a compound and a liquid dispersion medium, wherein said compound has a solubility greater than 30 mg/ml in said medium; and 
 ii) a microfluidizer capable of maintaining at least 25,000 PSI; 
   b) using a single pass exposure of said premix to said microfluidizer to create a population of nanoemulsion particles having diameters ranging approximately between 10-110 nm.   
     
     
         10 . The method of  claim 9 , wherein said dispersion medium is selected from the group consisting of aqueous media and oil-based media. 
     
     
         11 . The method of  claim 10 , wherein said aqueous media is selected from the group consisting of water, saline solution, ringers solution, dextrose, and short chain alcohols. 
     
     
         12 . The method of  claim 10 , wherein said oil-based media is selected from the group consisting of saturated and unsaturated oils from vegetable and marine sources, silicone oils, and mineral oils. 
     
     
         13 . The method of  claim 9 , wherein said compound is selected from the group consisting of a plant sterol, cod liver oil, tocopherol, lecithin, lutein, zeaxanthin, and soy protein. 
     
     
         14 . A method, comprising:
 a) providing;
 i) a premix comprising a compound, a first antioxidant, a second antioxidant, and an aqueous dispersion medium, wherein said compound has a solubility greater than 30 mg/ml in said medium; and 
 iii) a microfluidizer capable of maintaining at least 25,000 PSI; 
   c) using a single pass exposure of said premix to said microfluidizer to create a population of nanoemulsion particles having diameters ranging from between approximately 40-110 nm, wherein said particle diameter remains stable for at least four months.   
     
     
         15 . The method of  claim 14 , further comprising pasteurizing said population of nanoemulsion particles wherein said particle diameters remain stable. 
     
     
         16 . The method of  claim 14 , further comprising freezing said population of nanoemulsion particles wherein said particle diameters remain stable. 
     
     
         17 . A method, comprising;
 a) providing;
 i) a subject refractory to an administered compound at a therapeutically effective amount; 
 ii) a nanoemulsion comprising a population of particles encapsulating said compound, wherein said particles having diameters between approximately 10 and approximately 110 nanometers, wherein said nanoemulsion is not contaminated by particles having diameters larger than 110 nanometers; 
   b) delivering said nanoemulsion to said subjects under conditions such that said compound bioavailability is improved and wherein said compound is therapeutically effective.   
     
     
         18 . The method of  claim 17 , wherein said improved bioavailability comprises pharmacokinetic parameters selected from the group consisting of decreased T max , increased C max , and increased AUC. 
     
     
         19 . The method of  claim 17 , wherein said delivering comprises a method selected from the group consisting of oral, transdermal, intravenous, intraperitoneal, intramuscular, and subcutaneous. 
     
     
         20 . The method of  claim 17 , wherein said nanoemulsion comprises a plant sterol. 
     
     
         21 . The method of  claim 17 , wherein said nanoemulsion comprises lycopene. 
     
     
         22 . A nanoemulsion having bacteria-resistant properties, wherein said nanoemulsion comprises a population of particles encapsulating said compound, wherein said particles having diameters between approximately 10 and approximately 110 nanometers, wherein said nanoemulsion is not contaminated by particles having diameters larger than 110 nanometers. 
     
     
         23 . The nanoemulsion of  claim 22 , wherein said nanoemulsion resists bacterial growth for at least three months. 
     
     
         24 . The nanoemulsion of  claim 22 , wherein said bacterial-resistant properties comprise shear-force induced cell lysis. 
     
     
         25 . The nanoemulsion of  claim 22 , wherein said bacterial-resistant properties comprise an oxidizing environment. 
     
     
         26 . The nanoemulsion of  claim 22 , wherein said nanoemulsion is sterile. 
     
     
         27 . A method, comprising:
 a) providing;
 i) a premix comprising a compound and a liquid dispersion medium; and 
 ii) a device capable of creating a continuous turbulent flow under high pressure; 
   b) using said device to create a population of nanoemulsion particles having uniform diameter.   
     
     
         28 . The method of  claim 27 , wherein said dispersion medium is selected from the group consisting of aqueous media and oil-based media. 
     
     
         29 . The method of  claim 28 , wherein said aqueous media is selected from the group consisting of water, saline solution, ringers solution, dextrose, and short chain alcohols. 
     
     
         30 . The method of  claim 28 , wherein said oil-based media is selected from the group consisting of saturated and unsaturated oils from vegetable and marine sources, silicone oils, and mineral oils. 
     
     
         31 . The method of  claim 27 , wherein said compound is selected from the group consisting of a plant sterol, cod liver oil, tocopherol, lecithin, lutein, zeaxanthin, and soy protein.