TWI860511B - Nanoemulsion, method of forming the same, and application of using the same - Google Patents

Abstract

The present invention provides a nanoemulsion, a method of forming the same, and an application of using the same. The nanoemulsion is a W/O/W emulsion with a specific particle size and physical properties. The nanoeulsion can encapsulate lipid-soluble substances and water-soluble substances and has great permeability. Therefore, the nanoemulsion can be applied as oral drug delivery system, cosmetic composition and/or oral composition.

Description

Nanoemulsion, its preparation method and application

The present invention relates to a nanoemulsion and a method for producing the same, in particular to a W/O/W phase nanoemulsion, a method for producing the same and its application.

Nanoemulsion (NE) contains at least an oil phase, a water phase and a surfactant. When water, oil and a surfactant are mixed, oil droplets are dispersed in the water phase, i.e., oil-in-water (O/W) or water droplets are dispersed in the oil phase, i.e., water-in-oil (W/O), which are generally called emulsions. The nanoemulsion refers to an emulsion with an average particle size of less than 1000nm. Because the droplet size of nanoemulsion is small, the scattering ability of light is poor, so the appearance of nanoemulsion is usually transparent or translucent.

Currently, the carriers used to encapsulate active drugs are mainly water-in-oil type or oil-in-water type emulsions, which are relatively mature due to their relatively simple manufacturing process. However, water-in-oil type emulsions can only encapsulate fat-soluble active drugs, while oil-in-water type emulsions can only encapsulate water-soluble active drugs. In other words, the currently known water-in-oil type or oil-in-water type emulsions cannot have the function of encapsulating fat-soluble or water-soluble drugs at the same time.

Furthermore, in the application of cosmetics, most of the emulsion products on the market can only be used as film-type products. However, existing film-type products still have defects in penetration.

In view of this, there is an urgent need to provide a nanoemulsion that can be used as a carrier for simultaneously encapsulating fat-soluble drug components and water-soluble drug components, and can improve the application in cosmetics.

One aspect of the present invention is to provide a nanoemulsion, which comprises a first emulsion and a specific surfactant to form a W/O/W phase emulsion with a specific average particle size and physical properties.

Another aspect of the present invention is to provide an oral drug delivery system, which comprises the nanoemulsion of the above aspect and an active drug ingredient.

Another aspect of the present invention is to provide a cosmetic composition comprising the nanoemulsion of the above aspect.

Another aspect of the present invention is to provide an oral composition, which comprises the nanoemulsion of the above aspect and an active ingredient.

Another aspect of the present invention is to provide a method for producing a nanoemulsion, which comprises a step of homogenizing and emulsifying the homogenously mixed second emulsion to obtain the nanoemulsion.

According to one aspect of the present invention, a nanoemulsion is provided, which comprises a first emulsion and a surfactant. The first emulsion is a W/O phase emulsion. The surfactant comprises at least one of a cationic surfactant, an anionic surfactant and a non-ionic surfactant. The nanoemulsion is a W/O/W phase emulsion. The average particle size of the nanoemulsion is 20nm to 800nm. The oil-to-surfactant ratio (OSR) of the nanoemulsion is 0.4 to 0.8, and the polydispersity index (PDI) is less than 0.5.

According to one embodiment of the present invention, the cationic surfactant comprises dioctadecyldimethylammonium bromide (DODAB).

According to one embodiment of the present invention, the anionic surfactant comprises dihexadecyl phosphate (DHP).

According to one embodiment of the present invention, the non-ionic surfactant comprises saponin.

According to one embodiment of the present invention, the fluorescence polarization value of the above-mentioned nanoemulsion is 0.21 to 0.28.

According to another aspect of the present invention, an oral drug delivery system is provided, which comprises the nanoemulsion of the above aspect and an active drug ingredient. The active drug ingredient is a fat-soluble substance and/or a water-soluble substance.

According to another aspect of the present invention, a cosmetic composition is provided, which comprises the nanoemulsion of the above aspect. The dosage form of the cosmetic composition includes spray and film.

According to another aspect of the present invention, an oral composition is provided, which comprises the nanoemulsion of the above aspect and an active ingredient. The active ingredient is a hydrophilic ingredient and/or a lipophilic ingredient.

According to another aspect of the present invention, a method for preparing a nanoemulsion is provided. First, a first surfactant, oil and water are homogenously mixed to obtain a first emulsion. The first emulsion is a W/O phase emulsion. Next, the first emulsion and a second surfactant are homogenously mixed to obtain a second emulsion. Then, the second emulsion is subjected to a homogenization and emulsification step to obtain a nanoemulsion. The nanoemulsion is a W/O/W phase emulsion.

According to one embodiment of the present invention, the homogenization and emulsification step is performed for 20 to 40 minutes.

According to one embodiment of the present invention, the step of homogenously mixing the first surfactant, oil and water comprises performing the mixing at 15000 rpm for 10 to 15 minutes.

According to one embodiment of the present invention, the step of homogenously mixing the first emulsion and the second surfactant comprises performing the mixing at 15000 rpm for 10 to 15 minutes.

The nanoemulsion and its preparation method of the present invention are applied to the W/O/W phase emulsion with specific particle size and physical properties, which can be used as oral drug delivery systems, cosmetic compositions and/or oral compositions.

100:Methods

110,120,130: Operation

The following detailed description and accompanying drawings will provide a better understanding of the present disclosure. It should be noted that, as is standard practice in the industry, many features are not drawn to scale. In fact, for the sake of clarity of discussion, the dimensions of many features may be arbitrarily scaled.

[Figure 1] is a flow chart showing a method for preparing nanoemulsion according to some embodiments of the present invention.

[Figure 2A] to [Figure 2C] are transmission electron microscopy images of some embodiments of the present invention.

[Figure 3A] to [Figure 3C] are particle size distribution diagrams of some embodiments of the present invention.

As used in this disclosure, "around", "about", "approximately" or "substantially" generally means within 20%, within 10%, or within 5% of the stated value or range.

As mentioned above, the present invention provides a nanoemulsion and a method for preparing the same. The W/O/W phase emulsion prepared therefrom has specific particle size and physical properties and can be applied to oral drug delivery systems, cosmetic compositions and/or oral compositions.

Please refer to FIG. 1, which is a flow chart of a method 100 for manufacturing a nanoemulsion according to some embodiments of the present invention. First, operation 110 is performed to homogenously mix a first surfactant, oil, and water to obtain a first emulsion. In some embodiments, the first emulsion is a water-in-oil phase (W/O phase). In some embodiments, the first surfactant is sorbitan monooleate (Span80). In a specific example, operation 110 is to homogenize span80, evening primrose oil, and water. In some embodiments, operation 110 is to use a homogenizer to perform homogenous mixing at 15000 rpm for 10 to 15 minutes.

Then, operation 120 is performed to homogenize and mix the first emulsion and the second surfactant to obtain a second emulsion. In some embodiments, operation 120 is performed by using a homogenizer at 15000 rpm for 10 to 15 minutes. In some embodiments, the second surfactant includes at least one of a cationic surfactant, an anionic surfactant, and a non-ionic surfactant. The second surfactant can be selected according to application requirements. For example, if the application needs to be combined with an electrically charged biological product, a cationic surfactant or an anionic surfactant is selected; if the application is for food products, a non-ionic surfactant is selected. In one embodiment, the cationic surfactant comprises dioctadecyldimethylammonium bromide (DODAB). In another embodiment, the anionic surfactant comprises dihexadecyl phosphate (DHP). In yet another embodiment, the nonionic surfactant comprises saponin.

Then, operation 130 is performed to homogenize and emulsify the second emulsion to obtain a nanoemulsion. The obtained nanoemulsion is a W/O/W phase emulsion. In some embodiments, the average particle size of the nanoemulsion is 20nm to 800nm, preferably 20nm to 500nm, and more preferably 20nm to 200nm. The particle size of the nanoemulsion may affect subsequent applications. For example, if the particle size is too large (for example, greater than 800nm), its permeability is poor and it is less suitable for application in cosmetic compositions. The nanoemulsion of the present invention has specific physical properties, one of which is its polydispersity index (PDI). In some embodiments, the polydispersity index of the nanoemulsion is less than 0.5, preferably less than 0.3. The polydispersity index of the nanoemulsion of the present invention is small, which means that its particles are uniform and of similar size. On the contrary, if the dispersibility index of the nanoemulsion is large, for example, greater than 0.5, the particle size difference is large, which will make the stability and permeability of the nanoemulsion poor.

In some embodiments, the response surface methodology (RSM) can be used to optimize the homogenization emulsification step, and the central composite design (CCD) and the two-factor system of the three-level model can be used to obtain better homogenization emulsification setting conditions. In some embodiments, the homogenization emulsification step is performed for 20 minutes to 40 minutes, preferably 25 minutes to 35 minutes. If the emulsification time is too short (e.g., less than 20 minutes), a uniform W/O/W emulsion may not be obtained, and the resulting nanoemulsion particle size is too large to meet the use requirements; on the contrary, if the emulsification time is too long (e.g., greater than 40 minutes), the mixing effect cannot be improved, and only unnecessary energy and time costs are consumed.

The nanoemulsion of the present invention has another specific property, that is, its oil-to-surfactant ratio (OSR) is within a specific range. The oil-to-surfactant ratio of the nanoemulsion of the present invention is controlled to be 0.4 to 0.8, preferably 0.5 to 0.7, and more preferably 0.6. Generally speaking, if the OSR value is too high (for example, greater than 0.8) under a fixed oil content, the membrane fluidity will increase, resulting in loose arrangement between particles; conversely, if the OSR value is too low (for example, less than 0.4), the nanoemulsion will not have a better flow effect, and the fluidity in the membrane will decrease, and the particles will be tightly arranged. In other embodiments, the fluorescence polarization value of the nanoemulsion is 0.21 to 0.28. If the fluorescence polarization value is too high (for example, higher than 0.32), it may cause respiratory distress syndrome (RDS).

Since the nanoemulsion of the present invention is a W/O/W phase, it can simultaneously encapsulate fat-soluble and water-soluble active pharmaceutical ingredients. In other words, the nanoemulsion of the present invention can be used as an oral drug delivery system with fat-soluble and/or water-soluble active pharmaceutical ingredients. In addition, the nanoemulsion and active ingredients can also be used as oral compositions, and the active ingredients can be hydrophilic ingredients and/or lipophilic ingredients.

Furthermore, since the nanoemulsion of the present invention has better permeability, it can be used as one of the ingredients of cosmetics, and can be a spray-type or film-type cosmetic.

Several embodiments are used below to illustrate the application of the present invention, but they are not intended to limit the present invention. People with ordinary knowledge in the technical field of the present invention can make various changes and modifications without departing from the spirit and scope of the present invention.

Embodiment 1 to Embodiment 3

In Example 1, Span80, evening primrose oil and water were first mixed and the mixture was rotated at 15000 rpm for 10 minutes using a homogenizer to obtain a W/O phase coarse emulsion. Then, the W/O coarse emulsion was mixed with water and DODAB (cationic surfactant) was added, and the mixture was rotated at 15000 rpm for 15 minutes using a homogenizer. Then, homogenization and emulsification were performed for 30 minutes to obtain a W/O/W phase nanoemulsion.

The process of Example 2 and Example 3 is similar to that of Example 1, except that Example 2 replaces DODAB with DHP (anionic surfactant) and performs homogenization and emulsification for 28.53 minutes; while Example 3 replaces DODAB with saponin (nonionic surfactant) and performs homogenization and emulsification for 26.9 minutes. The OSR values of Examples 1 to 3 are all 60%.

Next, the particle size of the nanoemulsions of Examples 1 to 3 was observed using a transmission electron microscopy (TEM), as shown in Figures 2A to 2C. As can be seen from Figures 2A to 2C, the particle size of Example 1 is 110.26±1.2nm, the particle size of Example 2 is 168.5±2.4nm, and the particle size of Example 3 is 146.86±0.6nm. In addition, the particle size distribution and polydispersity index (PDI) of the nanoemulsions of Examples 1 to 3 were measured using dynamic light scattering (DLS), and the results are shown in Figures 3A to 3C. The PDI of Example 1 is 0.171±0.01, the PDI of Example 2 is 0.192±0.01, and the PDI of Example 3 is 0.222±0.01.

As can be seen from the enlarged image shown in FIG2A, the particles prepared by the present invention are indeed double-layer W/O/W phase nanoemulsions. Those with ordinary knowledge in the field should understand that W/O/W phase emulsions should be able to encapsulate fat-soluble and water-soluble substances at the same time.

According to the above embodiments, the nanoemulsion and its preparation method of the present invention, the W/O/W phase emulsion with specific particle size and physical properties can simultaneously encapsulate fat-soluble and water-soluble substances and has good permeability, so it can be applied to oral drug delivery systems, cosmetic compositions and/or oral compositions.

Although the present invention has been disclosed as above with several embodiments, they are not intended to limit the present invention. Anyone with ordinary knowledge in the technical field to which the present invention belongs can make various changes and modifications without departing from the spirit and scope of the present invention. Therefore, the scope of protection of the present invention shall be subject to the scope of the patent application attached hereto.

100:Methods

110,120,130: Operation

Claims (5)

A nanoemulsion comprises: a first emulsion, wherein the first emulsion is a W/O phase emulsion, and the W/O phase emulsion comprises a first surfactant, oil and water, wherein the first surfactant comprises sorbitan monooleate, and the oil comprises evening primrose oil; and a second surfactant, wherein the second surfactant comprises at least one of dioctadecyldimethylammonium bromide (DODAB) and dihexadecyl phosphate (DHP), wherein the nanoemulsion is a W/O/W phase emulsion, an average particle size of the nanoemulsion is 20 nm to 800 nm, the oil-to-surfactant ratio (OSR) of the first surfactant and the second surfactant is 0.4 to 0.8, and the polydispersity index (PDI) is 1.1 to 1.2. index, PDI) is less than 0.5. The nanoemulsion as described in claim 1, wherein the fluorescence polarization value of the nanoemulsion is 0.21 to 0.28. An oral drug delivery system comprising a nanoemulsion as described in any one of claims 1 to 2 and an active pharmaceutical ingredient, wherein the active pharmaceutical ingredient is a fat-soluble substance and/or a water-soluble substance. A cosmetic composition comprising the nanoemulsion as described in any one of claims 1 to 2, wherein a dosage form of the cosmetic composition includes a spray and a coating film. An oral composition comprising the nanoemulsion as described in any one of claims 1 to 2 and an active ingredient, wherein the active ingredient is a hydrophilic ingredient and/or a lipophilic ingredient.

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