Compositions and methods for making and using nanoemulsions
Inventors
NICOLOSI, Robert James • Wilson, Thomas
Assignees
University of Massachusetts Lowell
Publication Number
US-10016364-B2
Publication Date
2018-07-10
Expiration Date
2026-07-11
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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 Tmax, increased CmaX3 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.
Core Innovation
The invention discloses improved nanoemulsions characterized by a uniform and discrete range of very small particle diameters. These nanoemulsions are created using a process of microfluidization, which utilizes continuous turbulent flow at high pressures, typically with a single pass exposure. The process specifically involves mixing a substantially soluble compound into a heated dispersion medium before microfluidizing, resulting in nanoemulsions with narrow size distributions (for example, between approximately 10 and 110 nanometers) and a minimal presence of larger particles.
This uniformity in particle size leads to improved bioavailability of the incorporated compounds, such as pharmaceuticals, nutraceuticals, or cosmeceuticals. The improvement is quantifiable in terms of pharmacokinetic parameters, including decreased Tmax, increased Cmax, and increased area under the curve (AUC), compared to conventional formulations prepared by milling or grinding.
The patent addresses commercial and clinical needs by providing nanoemulsions that are resistant to bacterial growth and stable under extremes of temperature and pH. The resulting compositions thus exhibit significantly prolonged shelf life, enhanced stability, and improved ease of preparation without requiring organic solvents or polymers.
Claims Coverage
The independent claim presents one central inventive feature covering the method for preparing uniform nanoemulsions.
Method for making a uniform nanoemulsion by single-pass microfluidization
A method comprising: 1. Providing a premix containing: - an oil-based medium - an aqueous medium - an emulsifier - optionally, a compound to be delivered 2. Subjecting the premix to single-pass microfluidization using a microfluidizer. The method yields a uniform nanoemulsion having a population of nanoparticles such that: - Less than 3% of the nanoparticles are outside the diameter range of approximately 10 to 110 nanometers. - The difference between the minimum and maximum diameters of the nanoparticles does not exceed 600 nm.
The inventive feature centers on a method enabling the formation of highly uniform nanoemulsions using defined ingredients and single-pass microfluidization, resulting in nanoemulsions with a narrowly defined particle size distribution.
Stated Advantages
Improved bioavailability of incorporated compounds, as evidenced by pharmacokinetic parameters such as decreased Tmax, increased Cmax, and increased AUC.
Enhanced stability of nanoemulsions to extremes in both temperature and pH changes.
Bacterial-resistant and sterile properties extend the shelf-life of the nanoemulsions.
Ease and cost-effectiveness of preparation using microfluidization without requiring organic solvents or polymers.
Low viscosity and non-turbid formulations allow for better subject compliance and easier dispensing.
Ability for higher concentration formulations resulting in smaller dosage volumes.
Reduced required dosages and frequency due to greater absorption and bioavailability.
Documented Applications
Use as oral delivery vehicles for pharmaceuticals, nutraceuticals, and cosmeceuticals, including absorbable and non-absorbable compounds.
Administration of nanoemulsions via oral, transdermal, intravenous, intraperitoneal, intramuscular, or subcutaneous routes.
Formulation of bacteria-resistant and sterile preparations for improved product stability and safety.
Enhancement of dietary supplement formulations, such as plant sterols, cod liver oil, tocopherol, lutein, zeaxanthin, soy protein, DHA fish oil, and lycopene.
Use in beverages and foods as stable, low- or no-fat nanoemulsions for improved delivery of lipid-soluble nutrients.
Applications in diseases requiring improved bioavailability of active compounds, such as lowering cholesterol levels and treatment or prevention of macular degeneration.
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