Powder particulates comprising water-soluble polymer and production thereof by melt emulsification

Abstract

To provide powder particulates comprising a water-soluble polymer.SOLUTION: A composition comprises: a plurality of particulates comprising a water-soluble polymer and a plurality of nanoparticles. The water-soluble polymer is selected from the group consisting of polyvinyl alcohol (PVA), polyethylene oxide (PEO), polyethylene glycol (PEG), poly(lactide-co-glycolide) (PLGA), and any combination thereof. The water-soluble polymer defines at least an outer surface of the particulates, and at least a majority of the plurality of nanoparticles is disposed upon the outer surface.SELECTED DRAWING: Figure 2

Description

[Technical Field]

[0001] The present disclosure relates to powder particulates comprising water-soluble polymers. [Background technology]

[0002] Water-soluble polymers, including natural and synthetic polymers, are substances that dissolve, disperse, or swell in water and can modify the physical properties of aqueous systems by gelling, thickening, or emulsifying / stabilizing. Water-soluble polymers have a wide range of industrial uses, for example, as additives in products and applications such as food, pharmaceuticals (including as drug delivery vehicles), biomedical drugs, paints, textiles, paper, construction materials, adhesives, coatings, and water quality treatment. For example, polyvinyl alcohol is a polymer frequently used for drug delivery due to its rapid dissolution and ability to disperse or solubilize various substances therein.

[0003] It is sometimes desirable to utilize water-soluble polymers in particulate form. However, due to their hydrophilicity and high surface area, water-soluble polymer particulates can be difficult to handle. For example, water-soluble polymer particulates can clump together and / or be hygroscopic. Furthermore, when deployed in a product or application, water-soluble polymer particulates can dissolve more rapidly than desired. These problems can complicate the use of water-soluble polymer particulates in various products and applications. Summary of the Invention

[0004] FIELD OF THE DISCLOSURE The present disclosure relates generally to powder particulates comprising a water-soluble polymer, and more particularly to powder particulates comprising a water-soluble polymer and a surface additive that allows for tailoring of the particulate dissolution rate.

[0005] In some embodiments, the present disclosure provides a powder particle composition comprising a plurality of microparticles comprising a water-soluble polymer and a plurality of nanoparticles, wherein the water-soluble polymer defines at least an outer surface of the microparticles and at least a majority of the plurality of nanoparticles are disposed on the outer surface.

[0006] In some embodiments, the present disclosure provides a powder particulate composition comprising polyvinyl alcohol. The powder particulate composition includes a plurality of particulates comprising polyvinyl alcohol and a plurality of hydrophobically functionalized silica nanoparticles, wherein the polyvinyl alcohol defines at least an outer surface of the particulates, at least a majority of the plurality of silica nanoparticles are disposed on the outer surface, and the particulates are substantially spherical and have an average size (D) ranging from about 1 μm to about 150 μm. 50 ) with a geometric standard deviation (GSD) of about 3 or less.

[0007] In yet another embodiment, a method for making a powder particulate composition includes combining a water-soluble polymer and nanoparticles with a carrier fluid at a heated temperature above the melting point or softening temperature of the water-soluble polymer, wherein the water-soluble polymer and carrier fluid are substantially immiscible at the heated temperature; applying sufficient shear force in the presence of the nanoparticles to disperse the water-soluble polymer as liquefied droplets in the carrier fluid at the heated temperature; after the liquefied droplets are formed, cooling the carrier fluid to a temperature at which at least solidified microparticles are formed, wherein the microparticles comprise a water-soluble polymer and a plurality of nanoparticles, the water-soluble polymer defining at least an outer surface of the microparticle, and at least a majority of the plurality of nanoparticles being disposed on the outer surface; and separating the microparticles from the carrier fluid. [Brief explanation of the drawings]

[0008] The following figures are included to illustrate certain aspects of the present disclosure and should not be viewed as exclusive embodiments. The disclosed subject matter is capable of considerable modification, alteration, combination, and equivalents in form and function, as will occur to those skilled in the art and having the benefit of this disclosure. [Figure 1] FIG. 1 is a flow diagram of a non-limiting example method for producing powder particulates according to the present disclosure. [Figure 2] 1 shows an exemplary histogram of particle size of powder particulates obtained in Example 1. DETAILED DESCRIPTION OF THE INVENTION

[0009] FIELD OF THE DISCLOSURE The present disclosure relates generally to powder particulates comprising a water-soluble polymer, and more particularly to powder particulates comprising a water-soluble polymer and a surface additive that allows for tailoring of the particulate dissolution rate.

[0010] Advantageously, the present disclosure provides powder particulates comprising a water-soluble polymer that are much easier to handle than conventional water-soluble polymers, particularly in the form of powder particulates. The powder particulates include a plurality of particulates comprising a water-soluble polymer and a plurality of nanoparticles, the water-soluble polymer defining at least an outer surface of the particulates, and at least a majority of the nanoparticles being disposed on the outer surface. Surface coating of the nanoparticles can reduce handling problems and slow the dissolution rate of such powder particulates. Furthermore, by adjusting the loading of nanoparticles on the powder particulates, the dissolution rate can be tailored over a range of values.

[0011] Nanoparticles that facilitate tailored dissolution properties of water-soluble polymers can be easily incorporated onto the surface of powder microparticles through melt emulsification, as described in more detail herein. The loading of nanoparticles on powder microparticles can be easily adjusted during melt emulsification, and the loading of nanoparticles can further affect the size distribution of the resulting powder microparticles. Thus, melt emulsification can produce powder microparticles of water-soluble polymers over a range of particle sizes and dissolution rates. In certain instances, tailored incorporation of hydrophobic surface additives, such as hydrophobic silica, in the melt emulsification medium can facilitate control of the dissolution rate of water-soluble particles in water and improve the stability of powder microparticles in acidic environments. Higher surface coverage of powder particles can decrease the dissolution rate of the water-soluble polymer and increase the stability of powder microparticles.

[0012] More advantageously, the powder particles formed by melt-emulsification may have excellent shape regularity (substantially spherical) and narrow particle size distribution. Furthermore, the powder particles of the present disclosure may be easily sieved and exhibit good powder flow characteristics. Due to their shape regularity, the powder particles disclosed herein may be advantageous for use in various applications where strict particle size control is desirable, such as the pharmaceutical and biomedical industries.

[0013] The powder particulates of the present disclosure having these properties can be produced by a modified melt-emulsification process. Unlike traditional melt-emulsification processes, a sufficient amount of nanoparticles, particularly oxide nanoparticles, can be incorporated into the molten emulsification medium (carrier fluid) along with a water-soluble polymer so that a uniform coating of nanoparticles forms on the powder particulates when they solidify from the molten emulsification medium upon cooling. Silica nanoparticles, particularly hydrophobically functionalized silica nanoparticles, are among the oxide nanoparticles suitable for use in the present disclosure. The nanoparticles can function as emulsion stabilizers during melt-emulsification to form a coating on the powder particulates to improve powder flow characteristics and / or modify particle size distribution in a desired manner. Advantageously, the nanoparticle coating can provide good powder flow characteristics as a solid, provide a narrow particle size distribution, and provide controlled dissolution performance.

[0014] A further advantage of the present disclosure is that it eliminates the need to dry-blend nanoparticles with powder particulates in a separate blending process, thereby eliminating the need to define two separate particulate processing steps: 1) particulate formation and 2) particulate modification by dry blending. In contrast, traditional melt-emulsification processes may blend silica as a flow aid with the resulting particulates. Not only is this a process inefficient, but it can also result in poorly uniform coating and non-robust adhesion of the flow aid to the powder particulates. Inclusion of nanoparticles in the melt-emulsification medium according to the present disclosure can address these issues and provide related benefits, such as control of particulate size and dissolution rate. Because dry-blending processes do not incorporate a robust nanoparticle coating on the surface of the particulates, different particulate characteristics, such as performance differences during dissolution, aggregation, and size polydispersity, can result.

[0015] The terms used in the description and claims of this specification have their plain and ordinary meanings except as modified by the following paragraphs.

[0016] As used herein, the term "nanoparticle" refers to a particulate material having a particle size ranging from about 1 nm to about 500 nm.

[0017] As used herein, the term "oxide" refers to both metal oxides and non-metal oxides. For purposes of this disclosure, silicon is considered to be a metal.

[0018] As used herein, the term "oxide nanoparticles" refers to particulate materials having particle sizes ranging from about 1 nm to about 500 nm and comprising metal oxides or non-metal oxides.

[0019] As used herein, the terms "associated" and "association" between an emulsion stabilizer and a surface, and grammatical variations thereof, refer to chemical bonding and / or physical attachment of the emulsion stabilizer to the surface. Without being limited by theory, it is believed that the association described herein between the polymer and the emulsion stabilizer is primarily physical attachment via hydrogen bonding and / or other mechanisms. However, some chemical bonding may occur.

[0020] As used herein, the term "embedded" with respect to nanoparticles and the surface of a polymer particle refers to the nanoparticles extending at least partially into the surface such that the polymer is in contact with the nanoparticles to a greater extent than would occur if the nanoparticles were simply deposited on the surface of the polymer particle.

[0021] As used herein, "D 10 " refers to a diameter where 10% of the sample (by volume unless otherwise specified) is made up of particles having a diameter less than the diameter value in question. As used herein, "D 50 The term "D" refers to a diameter where 50% of the sample (by volume unless otherwise specified) is composed of particles having a diameter less than the diameter value in question. 50 may also be referred to as "average particle size." As used herein, "D 90 The term "diameter" refers to a diameter where 90% of the sample (by volume unless otherwise specified) is made up of particles having a diameter less than the diameter value in question.

[0022] As used herein, the terms "diameter span," "size span," and "span" refer to the breadth of a particle size distribution and are related by the relationship (D 90 -D 10 ) / D 50 (Again, unless otherwise specified, each D value is volume-based).

[0023] As used herein, the term "shear force" refers to stirring or similar processes that induce mechanical agitation in a fluid.

[0024] As used herein, the term "aspect ratio" refers to the length divided by the width, where the length is greater than the width.

[0025] FIG. 1 is a flow diagram of a non-limiting example method 100 for producing powder particulates according to the present disclosure. As shown, a water-soluble polymer 102, a carrier fluid 104, and an emulsion stabilizer 106 are combined 108 to produce a mixture 110. The water-soluble polymer 102, the carrier fluid 104, and the emulsion stabilizer 106 may be combined 108 individually or in a blend of components in any order, and the combining 108 process may include mixing and / or heating. In some examples, the carrier fluid 104 may be heated above the melting point or softening temperature of the water-soluble polymer 102 before combining the water-soluble polymer 102 and the emulsion stabilizer 106 therewith. The emulsion stabilizer 106 may include multiple nanoparticles, such as multiple oxide nanoparticles. One or more types of nanoparticles may be present in the emulsion stabilizer 106 in any combination and ratio.

[0026] Heating above the melting or softening temperature of the water-soluble polymer 102 can be at any temperature below the decomposition or boiling point of any of the components in the molten emulsion. Non-limiting examples include heating above the melting or softening temperature of the water-soluble polymer 102 by about 1°C to about 50°C, or about 1°C to about 25°C, or about 5°C to about 30°C, or about 20°C to about 50°C. In this disclosure, melting points can be determined by ASTM E794-06(2018) at heating and cooling rates of 10°C / min. The softening temperature or softening point of a polymer can be determined by ASTM D6090-17 unless otherwise specified. Softening points can be measured using a cup and ball apparatus available from Mettler-Toledo using a 0.50 gram sample at a heating rate of 1°C / min. Melting or softening temperatures in this disclosure can range from about 50°C to about 400°C.

[0027] The water-soluble polymer 102 may have a glass transition temperature (ASTM E1356-08(2014) with a heating and cooling rate of 10°C / min) of about -50°C to about 400°C, or about -50°C to about 0°C, or about -25°C to about 50°C, or about 0°C to about 150°C, or about 100°C to about 250°C, or about 150°C to about 300°C, or about 200°C to about 400°C. For example, the water-soluble polymer 102 may have a glass transition temperature (ASTM E1356-08(2014) with a heating and cooling rate of 10°C / min) of about 75°C to about 85°C.

[0028] The mixture 110 is then processed 112 by applying sufficient shear to produce liquefied droplets of the water-soluble polymer 102 at a temperature above the melting point or softening temperature of the water-soluble polymer 102, thereby forming a molten emulsion 114. Without being limited by theory, it is believed that, all other factors being equal, increasing the shear may reduce the size of the liquefied droplets in the carrier fluid 104. It should be understood that, at some point, there may be diminishing benefits to increasing the shear and thus reducing the droplet size, and / or breakdown into droplet contents may occur at higher shear rates, which reduces the quality of the microparticles produced therefrom. The optional addition of a surfactant may help stabilize the liquefied droplets by reducing coalescence with other liquefied droplets, thereby helping to maintain a narrow particle size distribution once the solidified microparticles are formed.

[0029] Examples of mixing devices that may be used to produce the molten emulsion 114 include, but are not limited to, extruders (e.g., continuous extruders, batch extruders, etc.), stirred reactors, blenders, reactors with in-line homogenizer systems, etc., and devices derived therefrom.

[0030] In non-limiting examples, the liquefied droplets can have a size of about 1 μm to about 1,000 μm, or about 1 μm to about 500 μm, or about 1 μm to about 150 μm, or about 1 μm to about 130 μm, or about 1 μm to about 100 μm, or about 10 μm to about 100 μm, or about 20 μm to about 80 μm, or about 20 μm to about 50 μm, or about 50 μm to about 90 μm. Particle size measurements can be performed by analysis of optical images or by using the built-in software of a Malvern MASTERSIZER 3000 AERO S instrument, which uses light scattering techniques for particle size measurement.

[0031] For light scattering techniques, a glass bead control sample with a diameter in the range of 15 μm to 150 μm under the trade name Quality Audit Standards QAS4002™ obtained from Malvern Analytical Ltd. may be used. Samples may be analyzed as dry powders dispersed in air using the dry powder dispersion module of a Mastersizer 3000 Aero S. Particle size may be derived using the instrument software from a plot of volume density as a function of size.

[0032] The molten emulsion 114 is then cooled 116 to solidify the liquefied droplets into solidified particles, also referred to herein as "powder particulates." The cooling rate can range from about 100°C / sec to about 10°C / hr, or from about 10°C / sec to about 10°C / hr, including any cooling rate therebetween. The shear force can be discontinued during cooling, or can be maintained at the same or a different rate during cooling. The cooled mixture 118 can then be processed 120 to isolate powder particulates 122 from other components 124 (e.g., carrier fluid 104, excess emulsion stabilizer 106, etc.). Washing, filtration, and / or the like can be performed at this stage to further purify the powder particulates 122. The powder particulates 122 include the water-soluble polymer 102 and at least a portion of the emulsion stabilizer 106 coating the exterior surface of the powder particulates 122. The nanoparticles and, optionally, surfactants can be associated with (disposed on) the exterior surface of the powder particulates 122. The emulsion stabilizer 106, or a portion thereof, may be deposited as a uniform coating on the powder particulates 122. In some cases, which may depend on factors such as, but not limited to, the temperature (including the cooling rate), the type of water-soluble polymer 102, and the type and size of the emulsion stabilizer 106, the nanoparticles of the emulsion stabilizer 106 may become at least partially embedded within the outer surface of the powder particulates 122 in the process of associating with the powder particulates 122. Even if embedding does not occur, the nanoparticles within the emulsion stabilizer 106 may remain robustly associated with the powder particulates 122, facilitating their further use. In contrast, dry-blending already formed powder particulates (e.g., formed by cryogenic grinding or precipitation processes) with a flow aid such as silica nanoparticles does not result in a robust, uniform coating of the flow aid on the powder particulates.

[0033] In the above, the water-soluble polymer 102 and carrier fluid 104 are selected so that these components are immiscible or substantially immiscible (<5% soluble by weight), particularly <1% soluble by weight, at various processing temperatures (e.g., from room temperature to temperatures at which liquefied droplets form and remain as two or more phases).

[0034] After separating the powder particulates 122 from the other components 124, further processing 126 of the powder particulates 122 may occur. In a non-limiting example, further processing 126 may include, for example, sieving the powder particulates 122 and / or blending the powder particulates 122 with other substances to form processed powder particulates 128. The processed powder particulates 128 may be formulated for use in a desired application.

[0035] Thus, the melt-emulsification process of the present disclosure may include combining a water-soluble polymer and nanoparticles with a carrier fluid at a heating temperature above the melting point or softening temperature of the water-soluble polymer, where the water-soluble polymer and carrier fluid are substantially immiscible at the heating temperature; applying sufficient shear to disperse the water-soluble polymer as liquefied droplets in the carrier fluid at the heating temperature in the presence of the nanoparticles; cooling the carrier fluid to a temperature at which at least solidified microparticles are formed after the liquefied droplets are formed, the microparticles comprising the water-soluble polymer and a plurality of nanoparticles, the water-soluble polymer defining at least an outer surface of the microparticles, and at least a majority of the plurality of nanoparticles disposed on the outer surface; and separating the microparticles from the carrier fluid. In such a process, the water-soluble polymer and carrier fluid are substantially immiscible at the heating temperature. In certain examples, the microparticles have a D of about 1 μm to about 150 μm, e.g., a size span of about 1.8 or less, e.g., a size span of about 0.5 to about 1.8. 50 Further, the microparticles may have a geometric standard deviation (GSD) of about 3 or less, for example, a GSD of about 1 to about 2.5, or about 1.2 to about 2.2, or about 1.2 to about 2.2, or about 1.2 to about 2.2.

[0036] The particle size is approximately 0.1 g / cm 3 ~Approx. 1.0g / cm 3 , or about 0.2 g / cm 3 ~about 0.8g / cm 3 , or about 0.4 g / cm 3 ~about 0.6g / cm 3 , or about 0.5 g / cm 3 ~about 0.6g / cm3 , or about 0.5 g / cm 3 ~about 0.8g / cm 3 The bulk density may be

[0037] Sufficient shear force to form liquefied droplets can be applied by stirring the carrier fluid in certain examples of the present disclosure. In non-limiting examples, the stirring speed can range from about 50 rotations per minute (RPM) to about 1500 RPM, or from about 250 RPM to about 1000 RPM, or from about 225 RPM to about 500 RPM, e.g., 100 RPM. The stirring speed while melting the water-soluble polymer can be the same or different from the stirring speed used after the liquefied droplets are formed. The liquefied droplets can be stirred for a stirring time of about 30 seconds to about 18 hours or more, or from about 1 minute to about 180 minutes, or from about 1 minute to about 60 minutes, or from about 5 minutes to about 6 minutes, or from about 5 minutes to about 30 minutes, or from about 10 minutes to about 30 minutes, or from about 30 minutes to about 60 minutes.

[0038] Water-soluble polymers (including copolymers) suitable for use in the present disclosure are not believed to be particularly limited. Suitable water-soluble polymers may include, for example, polyvinyl alcohol (PVA), polyethylene oxide (PEO), polyethylene glycol (PEG), poly(lactide-co-glycolide) (PLGA), or any combination thereof. Examples of polyvinyl alcohols suitable for use in the present disclosure may include, for example, POVAL™ 3-88, POVAL™ 5-88, POVAL™ 9-88, and POVAL™ 7-92. Some examples of water-soluble polymers may be suitable for use in the pharmaceutical and biomedical industries. Other water-soluble polymers more suitable for other applications may be selected as needed.

[0039] The loading (concentration) of the water-soluble polymer in the carrier fluid can vary over a wide range. The loading in the carrier fluid can play at least some role in determining the properties of the resulting microparticles after solidification of the liquefied droplets. In a non-limiting example, the loading of the water-soluble polymer in the carrier fluid can range from about 1% to about 99% by weight, based on the weight of the carrier fluid. In more specific examples, the loading of the water-soluble polymer can range from about 5% to about 75% by weight, or from about 10% to about 60% by weight, or from about 20% to about 50% by weight, or from about 20% to about 30% by weight, or from about 30% to about 40% by weight, or from about 40% to about 50% by weight, or from about 50% to about 60% by weight. The water-soluble polymer may be present in an amount ranging from about 5% to about 60% by weight, or from about 5% to about 25% by weight, or from about 10% to about 30% by weight, or from about 20% to about 45% by weight, or from about 25% to about 50% by weight, or from about 40% to about 60% by weight (solids loading), based on the combined amount of water-soluble polymer and carrier fluid.

[0040] Various nanoparticles, particularly oxide nanoparticles, may be suitable for use in forming the powder particulates of the present disclosure. Among the oxide nanoparticles that may be suitable for use in the present disclosure include, for example, silica nanoparticles, titania nanoparticles, zirconia nanoparticles, alumina nanoparticles, iron oxide nanoparticles, copper oxide nanoparticles, tin oxide nanoparticles, boron oxide nanoparticles, cerium oxide nanoparticles, thallium oxide nanoparticles, tungsten oxide nanoparticles, or any combination thereof. Mixed oxides, such as aluminosilicates, borosilicates, and aluminoborosilicates, are also encompassed by the term "oxide." Oxide nanoparticles may be hydrophilic or hydrophobic, which may be inherent to the nanoparticles or may result from a surface treatment of the nanoparticles. For example, silica nanoparticles with hydrophobic surface treatments, such as dimethylsilyl, trimethylsilyl, and the like, may be formed by reacting hydrophilic surface hydroxyl groups. Hydrophobically functionalized oxide nanoparticles may be desirable in the methods and compositions of the present disclosure to reduce the dissolution rate of water-soluble polymers in the powder particulates. Non-functionalized oxide nanoparticles may also be suitable for use.

[0041] Silica nanoparticles, particularly fumed silica nanoparticles having hydrophobic functionalization thereon, may be particularly suitable for use in the present disclosure due to the availability of various functionalized silicas, varying in the type of hydrophobic functionalization and particle size. Silazane and silane are easy hydrophobic functionalizations that can be used in the present disclosure. Thus, the oxide nanoparticles used in the present disclosure may comprise or essentially consist of silica nanoparticles, particularly silica nanoparticles that are hydrophobically functionalized. Silica nanoparticles may also be used in combination with other types of oxide or non-oxide nanoparticles when the other types of oxide or non-oxide nanoparticles can impart properties to the particulate or object formed therefrom that are not achieved when silica nanoparticles are used alone.

[0042] Carbon black is another type of nanoparticle that may be present as an emulsion stabilizer in the compositions and methods disclosed herein. Various grades of carbon black are well known to those skilled in the art, any of which may be used herein.

[0043] Polymer nanoparticles are another type of nanoparticle that can be used as an emulsion stabilizer in the present disclosure. Suitable polymer nanoparticles can include one or more polymers that are thermosetting and / or crosslinked so that they do not melt when processed by melt emulsification according to the present disclosure. Crosslinked fluorinated polymers can be suitable in this regard. High molecular weight thermoplastic polymers with high melting or decomposition points can also be suitable polymer nanoparticle emulsion stabilizers.

[0044] When forming powder particulates according to the present disclosure, the silica nanoparticle loading (concentration) and particle size can be varied over a wide range, and the silica or other nanoparticle loading and particle size can play at least some role in determining the properties of the resulting particulates after solidification of the liquefied droplets.

[0045] In non-limiting examples, the loading of silica nanoparticles in the carrier fluid can range from about 0.01 wt% to about 20 wt%, or from about 0.05 wt% to about 15 wt%, or from about 0.05 wt% to about 10 wt%, or from about 0.05 wt% to about 5 wt%, based on the weight of the water-soluble polymer. In more specific examples, the loading of silica nanoparticles can range from about 0.01 wt% to about 5 wt%, or from about 0.05 wt% to about 2 wt%, or from about 0.1 wt% to about 1.5 wt%, or from about 0.2 wt% to about 1.0 wt%, or from about 0.25 wt% to about 1 wt%, or from about 0.25 wt% to about 0.5 wt%, or from about 0.05 wt% to about 1 wt%. Other types of nanoparticles, particularly oxide nanoparticles, can be used in similar loading ranges. The loading of nanoparticles in the powder particulates can also be within these ranges.

[0046] In non-limiting examples, the particle size of the silica nanoparticles can range from about 1 nm to about 150 nm, or from about 1 nm to about 100 nm. In some cases, the particle size of the silica nanoparticles can be up to 500 nm. In more specific examples, the particle size of the silica nanoparticles can range from about 2 nm to about 150 nm, from about 5 nm to about 75 nm, from about 5 nm to about 50 nm, from about 5 nm to about 10 nm, from about 10 nm to about 20 nm, from about 20 nm to about 30 nm, from about 30 nm to about 40 nm, from about 40 nm to about 50 nm, or from about 50 nm to about 60 nm. Other types of nanoparticles, particularly oxide nanoparticles, can be used in similar size ranges.

[0047] Nanoparticles, especially silica nanoparticles and other oxide nanoparticles, have a particle size of about 10 m 2 / g~about 500m 2 / g, or approximately 10 m 2 / g~about 150m 2 / g, or approximately 25m 2 / g~about 100m 2 / g, or approximately 100m 2 / g ~ approx. 250m 2 / g, or approximately 250m 2 / g~about 500m 2 / g BET surface area.

[0048] Certain silica nanoparticles suitable for use in the present disclosure may be hydrophobically functionalized. Such hydrophobic functionalization may render the silica nanoparticles less compatible with water than unfunctionalized silica nanoparticles. In addition, hydrophobic functionalization may improve the dispersion of silica nanoparticles in carrier fluids that may be highly hydrophobic. The hydrophobic functionalization may be non-covalently or covalently attached to the surface of the silica nanoparticles. Covalent attachment may be achieved, for example, by functionalizing surface hydroxyl groups on the surface of the silica nanoparticles. In a non-limiting example, silica nanoparticles may be treated with hexamethyldisilazane to result in covalent hydrophobic functionalization. Commercially available hydrophobically functionalized silica nanoparticles include, for example, AEROSIL® RX-50 (Evonik, average particle size = 40 nm) and AEROSIL® R-812S (Evonik, average particle size = 7 nm).

[0049] However, it should be understood that non-functionalized silica nanoparticles may also be suitable for use as emulsion stabilizers in the present disclosure.

[0050] When forming powder particulates according to the present disclosure, at least a portion of the nanoparticles, such as silica nanoparticles, can be disposed as a coating on the outer surface of the powder particulate. The coating can be substantially uniformly disposed on the outer surface as assessed by visual observation of the particulate. As used herein with respect to a coating, the term "substantially uniform" refers to a uniform coating thickness across the surface locations covered by the nanoparticles, particularly the entire outer surface. The coverage of the coating, including nanoparticles, on the powder particulate can range from about 5% to about 100%, or from about 5% to about 25%, or from about 20% to about 50%, or from about 40% to about 70%, or from about 50% to about 80%, or from about 60% to about 90%, or from about 70% to about 100% of the surface area of ​​the particulate. The coverage can be determined by image analysis of SEM micrographs. The water-soluble polymer can comprise about 90% to about 99.5% by weight of the powder particulates disclosed herein.

[0051] The microparticles of the present disclosure may comprise from about 0.05% to about 5% by weight, or from about 0.05% to about 4.5% by weight, or from about 0.1% to about 4% by weight, or from about 0.15% to about 3.5% by weight of silica nanoparticles. Other types of nanoparticles suitable for use as emulsion stabilizers may be present on the microparticles at similar loadings.

[0052] Suitable carrier fluids for use in the present disclosure include those in which the water-soluble polymer is substantially immiscible with the carrier fluid, the carrier fluid has a boiling point above the melting or softening temperature of the water-soluble polymer, and the carrier fluid has sufficient viscosity to form substantially spherical liquefied droplets when the water-soluble polymer is melted or softened therein. Suitable carrier fluids may include, for example, silicone oils, fluorinated silicone oils, perfluorinated silicone oils, polyethylene glycol, alkyl-terminated polyethylene glycols (e.g., C1-C4 terminal alkyl groups such as tetraethylene glycol dimethyl ether (TDG)), paraffin, liquid petrolatum, mink oil, turtle oil, soybean oil, perhydrosqualene, sweet almond oil, carophyllum oil, palm oil, pearl oil, grapeseed oil, sesame oil, corn oil, rapeseed oil, sunflower oil, cottonseed oil, apricot oil, castor oil, avocado oil, jojoba oil, olive oil, cereal germ oil, esters of lanolin acid, esters of oleic acid, esters of lauric acid, esters of stearic acid, fatty esters, higher fatty acids, fatty alcohols, fatty acid-modified polysiloxanes, fatty alcohol-modified polysiloxanes, polyoxyalkylene-modified polysiloxanes, and the like, and any combination thereof.

[0053] A suitable carrier fluid has a density of about 0.6 g / cm 3 ~Approx. 1.5g / cm 3 and the water soluble polymer may have a density of about 0.7 g / cm 3 ~Approx. 1.7g / cm 3 and the water-soluble polymer has a density similar to, lower than, or higher than the density of the carrier fluid.

[0054] Particularly suitable silicone oils are polysiloxanes. Exemplary silicone oils suitable for use in the present disclosure include, for example, polydimethylsiloxane (PDMS), methylphenylpolysiloxane, alkyl-modified polydimethylsiloxane, alkyl-modified methylphenylpolysiloxane, amino-modified polydimethylsiloxane, amino-modified methylphenylpolysiloxane, fluorine-modified polydimethylsiloxane, fluorine-modified methylphenylpolysiloxane, polyether-modified polydimethylsiloxane, polyether-modified methylphenylpolysiloxane, and the like, and any combination thereof.

[0055] In a non-limiting example, the carrier fluid and water-soluble polymer may be heated to a temperature of about 200°C or greater. A suitable heating temperature may be selected based on the melting or softening temperature of the water-soluble polymer and the boiling point of the carrier fluid. The cooling rate after formation of the liquefied polymer droplets may be varied as desired. In some cases, cooling may occur after heating is discontinued, with heat dissipation to the surrounding environment occurring at a natural (uncontrolled) rate. In other cases, cooling at a controlled rate (e.g., gradually reducing the heating temperature and / or using jacketed temperature control to increase or decrease the cooling rate) may be employed.

[0056] Carrier fluids such as polysiloxanes, including PDMS, can have a viscosity of from about 1,000 cSt to about 150,000 cSt, or from about 1,000 cSt to about 60,000 cSt, or from about 40,000 cSt to about 100,000 cSt, or from about 75,000 cSt to about 150,000 cSt at 25° C. The viscosity of the carrier fluid can be obtained from commercial sources or, if desired, can be measured by techniques known to those skilled in the art.

[0057] Separating the powder particles from the carrier fluid can be accomplished by any of a variety of known separation techniques. The powder particles can be separated from the carrier fluid using any of gravity settling and filtration, decantation, centrifugation, etc. The powder particles can be washed with a solvent in which the carrier fluid is soluble and the powder particles are insoluble during the separation process. Additionally, a solvent in which the carrier fluid is soluble and the powder particles are insoluble can be mixed with the carrier fluid and the powder particles prior to initially separating the powder particles from the carrier fluid.

[0058] Suitable solvents for washing the powder particulates or mixing with the carrier fluid may include, but are not limited to, aromatic hydrocarbons (e.g., toluene and / or xylene), aliphatic hydrocarbons (e.g., heptane, n-hexane, and / or n-octane), cyclic hydrocarbons (e.g., cyclopentane, cyclohexane, and / or cyclooctane), ethers (e.g., diethyl ether, tetrahydrofuran, diisopropyl ether, and / or dioxane), halogenated hydrocarbons (e.g., dichloroethane, trichloroethane, dichloromethane, chloroform, and / or carbon tetrachloride), alcohols (e.g., methanol, ethanol, isopropanol, and / or n-propanol), ketones (e.g., methyl ethyl ketone and / or acetone); esters (e.g., ethyl acetate, etc.), water, and the like, and any combination thereof.

[0059] After washing the powder particles, they may be either heated, vacuum dried, air dried, or any combination thereof.

[0060] Advantageously, the carrier fluids and wash solvents of the systems and methods described herein are renewable and reusable, if desired.

[0061] Even when powder particulates are washed with a solvent, in some cases, a limited amount of carrier fluid may remain. In a non-limiting example, any of the powder particulates of the present disclosure may contain a non-zero amount of carrier fluid of up to about 5% by weight that remains associated with a plurality of powder particulates. The carrier fluid may be associated with the outer surface of the powder particulate and / or trapped within voids or cavities within the powder particulate. The amount of voids present may affect the dissolution rate as well as the amount of carrier fluid retained by the particulate. When they occur, up to about 35% by volume of voids, or up to about 20% by volume of voids, or up to about 10% by volume of voids, or up to about 5% by volume of voids may be present in the powder particulate, and the voids may be filled or unfilled.

[0062] At least a majority of the powder particulates obtained according to the present disclosure may be substantially spherical in shape. More typically, about 90% or more, or about 95% or more, or about 99% or more of the powder particulates produced by melt-emulsification according to the present disclosure may be substantially spherical in shape. In a non-limiting example, the powder particulates of the present disclosure may have a sphericity (circularity) of about 0.9 or greater, including about 0.90 to about 1.0, or about 0.93 to about 0.99, or about 0.95 to about 0.99, or about 0.97 to about 0.99, or about 0.98 to about 1.0. Sphericity (circularity) may be measured using a Sysmex FPIA-2100 Flow Particle Image Analyzer. To determine circularity, an optical microscope image of the particulates is taken. Calculate the perimeter (P) and area (A) of the microparticle in the plane of the microscope image (e.g., using a Sysmex FPIA 3000 Particle Shape and Size Analyzer, available from Malvern Instruments). The circularity of the microparticle is calculated as C EA / P and C EA is the circumference of a circle with an area equivalent to the area of ​​the actual particle (A).

[0063] The powder particulates of the present disclosure may have an angle of repose of about 25° to about 45°, or about 25° to about 35°, or about 30° to about 40°, or about 35° to about 45°. The angle of repose may be determined using ASTM D6393-14 "Standard Test Method for Bulk Solids" Characterized by Carr Indices" using a Hosokawa Micron Powder Characteristics Tester PT-R.

[0064] Additionally, powder particulates formed in accordance with the present disclosure may have a plurality of silica or other nanoparticles at least partially embedded in the outer surface defined by the water-soluble polymer. When silica or other nanoparticles are at least partially embedded in the outer surface, portions of the nanoparticle structure may be located within craters or depressions in the outer surface, thereby making the nanoparticles more difficult to remove from the surface. It should be understood that even if substantial embedding does not occur, appropriately functionalized nanoparticles, such as hydrophobically functionalized silica nanoparticles, may associate non-covalently (e.g., via van der Waals-type interactions) to promote retention of the nanoparticles on the outer surface.

[0065] Powder particles isolated from the carrier fluid according to the above disclosure can be further processed to produce powder particles suitable for the intended application. In some instances, the powder particles can be passed through a sieve or similar structure having an effective screening size larger than the average particle size of the powder particles. For example, an exemplary screening size for processing powder particles can be about 150 μm. When referring to sieving, the pore / screen size is described by the USA Standard Sieve (ASTM E11-17). Other screening sizes, larger or smaller, may be more suitable for particles intended for use in various applications. Sieving can remove larger particles that may be formed during the melt-emulsification process and / or remove agglomerated particles that may have poor flow characteristics. Generally, sieves having an effective screening size ranging from about 10 μm to about 250 μm can be used.

[0066] Additionally, the powder particles that pass through a sieve or similar structure can be mixed with one or more additional components, such as flow aids, fillers, or other substances intended to tailor the properties of the powder particles for the intended use. Mixing the additional components with the powder particles can be performed by dry blending techniques. Suitable examples of flow aids (e.g., carbon black, graphite, silica, etc.) and similar materials are well known to those skilled in the art.

[0067] In view of the above, the present disclosure further provides a composition comprising a powder particulate bearing a coating comprising nanoparticles, particularly oxide nanoparticles. The composition can include a plurality of particulates comprising a water-soluble polymer and a plurality of nanoparticles, particularly oxide nanoparticles, wherein the water-soluble polymer defines at least an outer surface of the particulate, and the plurality of nanoparticles are disposed on the outer surface. In certain embodiments, the particulates have a D in the range of about 1 μm to about 150 μm. 50 and may have a geometric standard deviation (GSD) of about 3 or less, or from about 0.5 to about 3, or from about 0.75 to about 2.75, or from about 1 to about 2.5, or from about 1.25 to about 2.25, or from about 1.5 to about 2.

[0068] As discussed herein, the nanoparticles on the outer surface of the powder particulates can be metallic or non-metallic nanoparticles, particularly silica nanoparticles or other oxide nanoparticles. Silica nanoparticles bearing hydrophobic functionalization, either alone or in combination with other types of nanoparticles, can be particularly desirable as emulsion stabilizers that become associated with the outer surface of the powder particulates.

[0069] The size of the powder particulates that can be produced in accordance with the disclosure herein is not believed to be particularly limited, but may be 125 μm or less in size, or 100 μm or less in size, about 150 μm or less in size to facilitate use in various applications such as three-dimensional printing or other types of applications in which particulates are used. Particularly suitable powder particulates, as mentioned above, range in size from about 1 μm to about 150 μm. 50 Particle size measurements may be performed using a Malvern MASTERSIZER 3000 AERO S instrument. Various factors, such as the size, type, and loading of nanoparticles, shear rate, heating temperature, cooling rate, carrier fluid and its viscosity, and the particular water-soluble polymer used, may also affect the size and / or particle size distribution of the powder particulates obtained in accordance with the present disclosure, by way of non-limiting example. One or more of these factors may also determine the sphericity of the powder particulates and / or whether a non-zero amount of carrier fluid is retained within the powder particulates.

[0070] In yet additional non-limiting embodiments, the compositions disclosed herein can further include flow aids or additional ingredients that can facilitate use of the powder particulates in the desired application, suitable examples of each being well known to those skilled in the art.

[0071] Any of the powder particulates disclosed herein can be formulated into compositions suitable for pharmaceutical and biomedical applications, such as by slowing the polymer dissolution rate (e.g., as a solubility modifier in tablet formulations) to modify the release rate of a drug. Other uses for the powder particulates of the present disclosure can include, but are not limited to, water-soluble drug / therapeutic agent matrices, water-dispersible pesticide granules, dissolution-controlled powders for 3D printing (e.g., for powder bed fusion), and dissolution-controlled microparticles in paint formulations.

[0072] Embodiments disclosed herein include the following. A. Powdered Particulate Compositions. The powdered particulate compositions include a plurality of particulates comprising a water-soluble polymer and a plurality of nanoparticles, the water-soluble polymer defining at least an outer surface of the particulates, and at least a majority of the plurality of nanoparticles disposed on the outer surface. B. A powder particulate composition comprising polyvinyl alcohol. The powder particulate composition includes a plurality of particulates comprising polyvinyl alcohol and a plurality of silica nanoparticles that are hydrophobically functionalized, wherein the polyvinyl alcohol defines at least an outer surface of the particulates, at least a majority of the plurality of silica nanoparticles are disposed on the outer surface, and the particulates are substantially spherical and have an average size (D) ranging from about 1 μm to about 150 μm. 50 ) with a geometric standard deviation (GSD) of about 3 or less. C. A method for making a powder particulate composition, the method comprising: combining a water-soluble polymer and nanoparticles with a carrier fluid at a heated temperature above the melting point or softening temperature of the water-soluble polymer, wherein the water-soluble polymer and carrier fluid are substantially immiscible at the heated temperature; applying a shear force sufficient to disperse the water-soluble polymer as liquefied droplets in the carrier fluid at the heated temperature in the presence of the nanoparticles; after the liquefied droplets are formed, cooling the carrier fluid to a temperature at which at least solidified microparticles are formed, the microparticles comprising the water-soluble polymer and a plurality of nanoparticles, the water-soluble polymer defining at least an outer surface of the microparticles, and at least a majority of the plurality of nanoparticles disposed on the outer surface; and separating the microparticles from the carrier fluid.

[0073] Embodiments A, B, and C may include one or more of the following elements in any combination. Element 1: The water-soluble polymer is selected from the group consisting of polyvinyl alcohol (PVA), polyethylene oxide (PEO), polyethylene glycol (PEG), poly(lactide-co-glycolide) (PLGA), and any combination thereof. Element 2: The water-soluble polymer includes polyvinyl alcohol (PVA). Element 3: The plurality of nanoparticles comprises or consists essentially of a plurality of oxide nanoparticles, carbon black, or any combination thereof. Element 4: The plurality of nanoparticles includes silica nanoparticles. Element 5: Silica nanoparticles have a D in the range of about 2 nm to about 150 nm 50 It has. Element 6: The plurality of nanoparticles are hydrophobically functionalized. Element 7: At least a majority of the plurality of microparticles are substantially spherical in shape, and D 50 However, the range is from about 1 μm to about 150 μm. Element 8: The plurality of microparticles have a circularity of about 0.9 to about 1. Element 9: The plurality of microparticles comprises about 0.05% to about 5% by weight of nanoparticles.

[0074] As a non-limiting example, exemplary combinations applicable to A, B, and C include, but are not limited to, 1 or 2, and 3; 1 or 2, and 4; 1 or 2, 4 and 5; 1 or 2, and 6; 1 or 2, and 7; 1 or 2, and 8; 1 or 2, 4 and 9; 1 or 2, 4 and 6; 1 or 2, 7 and 8; 3 or 4, and 5; 3 or 4, and 6; 3 or 4, and 7; 3 or 4, and 8; 3 or 4, and 9; 4 and 5, and 6; 4 and 5, and 7; 4 and 5, and 8; 4 and 5, and 9; 6 and 7; 6 and 8; 6 and 9; 7 and 8; 7 and 9; and 8 and 9.

[0075] To facilitate a better understanding of embodiments of the present disclosure, the following examples of preferred or representative embodiments are given, which should in no way be read as limiting or defining the scope of the present disclosure. [Example]

[0076] In the following examples, the average particle size (D 50 ), D 10 , and D 90 Measurements were made using a Malvern MASTERSIZER 3000 particle size analyzer.

[0077] The water-soluble polymers were compounded by melt mixing in a HAAKE™ RHEOMIX batch mixer equipped with a high shear rotor.

[0078] POVAL™ 5-88 (a partially hydrolyzed (approximately 88% hydrolyzed), semi-crystalline polyvinyl alcohol (PVA) polymer with a melting point of 220° C., available from Kuraray) was used to form the powder particulates in the following disclosure. AEROSIL® RX-50 (a hydrophobic specialty fumed silica treated with hexamethyldisilazane (HMDS), available from Evonik) was used as an emulsion stabilizer.

[0079] Three types of powdered microparticles were prepared: (1) virgin particles containing PVA without any AEROSIL® RX-50 treatment (Comparative Example 1), (2) particles containing PVA with 0.5% w / w AEROSIL® RX-50 (Example 1), and (3) microparticles containing PVA with 1.0% w / w AEROSIL® RX-50 (Example 2).

[0080] Comparative Example 1. PVA Powder Microparticles. In this example, virgin POVAL™ 5-88 was used. Approximately 35.0 g of PDMS with a kinematic viscosity of 60,000 cSt was added to a HAAKE™ RHEOMIX batch mixer and mixed at 100 RPM for 5 minutes at 240°C. 15 g of PVA was slowly dosed into the extruder over 2-3 minutes. After complete addition of the PVA, the mixer was sealed and mixed for 10 minutes to form dispersed microparticles. The resulting slurry was then dumped onto dry ice and washed with heptane. The powder microparticles were highly granular and could not be sieved through a 150 μm sieve.

[0081] Example 1. PVA powder microparticles coated with 0.5% w / w AEROSIL® RX-50. Silica-coated powder microparticles were prepared in the same manner as Comparative Example 1, except that 0.07 g of AEROSIL® RX-50 silica nanoparticles were mixed with PDMS before adding the PVA. The resulting powder microparticles were sievable and exhibited a narrow particle size distribution. Figure 2 shows an exemplary histogram of particle sizes for the powder microparticles obtained in Example 1.

[0082] Example 2. PVA powder microparticles coated with 1.0% w / w AEROSIL® RX-50. Example 1 was repeated with a higher loading of AEROSIL® RX-50 (0.15 g).

[0083] Dissolution Properties. The dissolution properties of the three aforementioned powder particulate samples were determined by combining 0.125 g of the powder particulate with water and observing the dissolution rate over time. At 5 minutes, partial dissolution of the uncoated powder particulate (Comparative Example 1) was evident, while no dissolution was observed for the coated powder particulates (Examples 1 and 2). At 3 hours, all three samples had completely dissolved, although the uncoated powder particulates produced a cloudier solution than the coated particulates.

[0084] All documents described herein are incorporated by reference for purposes of all jurisdictions where such practice is permitted, including any priority documents and / or testing procedures to the extent not inconsistent with this text. While forms of the disclosure have been illustrated and described, as is apparent from the foregoing general description and specific embodiments, various modifications can be made without departing from the spirit and scope of the disclosure. Accordingly, the disclosure is not intended to be limited thereby. For example, the compositions described herein may not include any component or composition not expressly listed or disclosed herein. Any method may lack any step not listed or disclosed herein. Similarly, the term "comprising" is considered synonymous with the term "including." Whenever a method, composition, element, or group of elements is preceded by the transitional phrase "comprising," it is understood that the inventors also contemplate the same composition or group of elements with the transitional phrase "consisting essentially of," "consisting of," "selected from the group consisting of," or "is" preceding the composition, element, or list of elements, and vice versa.

[0085] Unless otherwise indicated, all numbers expressing quantities of ingredients, properties such as molecular weight, reaction conditions, and the like used in this specification and the related claims are to be understood as being modified in all instances by the term "about." Accordingly, unless indicated to the contrary, the numerical parameters set forth in the following specification and appended claims are approximations that may vary depending upon the desired properties sought to be obtained by embodiments of the present invention. At the very least, and without attempting to limit the application of the doctrine of equivalents to the scope of the claims, each numerical parameter should be construed in light of the number of reported significant digits and by applying ordinary rounding techniques.

[0086] Whenever a numerical range with a lower and upper limit is disclosed, any number within that range and any included range is specifically disclosed. In particular, all ranges of values ​​disclosed herein (in the form "from about a to about b," or, equivalently, "from approximately a to b," or, equivalently, "from approximately a to b") should be understood to describe all numbers and ranges encompassed within the broader range of values. Furthermore, terms in the claims have their plain and ordinary meaning unless expressly and unambiguously defined otherwise by the patentee. Additionally, when used in the claims, the indefinite articles "a" or "an" are defined herein to mean one or more than one of the element they introduce.

[0087] One or more exemplary embodiments are presented herein. For clarity, not all features of a physical implementation are described or illustrated in this application. It is understood that in developing a physical embodiment of the present disclosure, numerous implementation-specific decisions must be made to achieve the developer's goals, which may vary from implementation to implementation and from time to time, such as compliance with system-related, business-related, government-related, and other constraints. While the developer's efforts may be time-consuming, such efforts would nevertheless be routine for one of ordinary skill in the art having the benefit of this disclosure.

[0088] Thus, the present disclosure is well adapted to achieve the ends and advantages mentioned, as well as those inherent therein. The specific embodiments described above are illustrative only, as the disclosure may be modified and practiced in different but equivalent manners apparent to those skilled in the art having the benefit of the teachings herein. Furthermore, no limitations are intended to the details of construction or design shown herein, other than as described in the following claims. It is therefore evident that the specific exemplary embodiments disclosed above may be altered, combined, or modified, and all such variations are considered within the scope and spirit of the present disclosure. The illustratively disclosed embodiments preferably may be practiced in the absence of any element not specifically disclosed herein and / or any optional element disclosed herein.

Claims

1. A composition comprising a water-soluble polymer and a plurality of microparticles containing a plurality of nanoparticles, wherein the water-soluble polymer defines at least the outer surface of the microparticles, and at least most of the plurality of nanoparticles are disposed on the outer surface. The composition is The composition wherein the microparticles are in the size range of about 20 μm to about 150 μm.

2. The composition according to claim 1, wherein the water-soluble polymer is selected from the group consisting of polyvinyl alcohol (PVA), polyethylene oxide (PEO), polyethylene glycol (PEG), poly(lactide-co-glycolide) (PLGA), and any combination thereof.

3. The composition according to claim 1, wherein the water-soluble polymer contains polyvinyl alcohol (PVA).

4. The composition according to claim 1, wherein the plurality of nanoparticles comprises, consists essentially of, or consists of a plurality of oxide nanoparticles, carbon black, or any combination thereof.

5. The composition according to claim 1, wherein the plurality of nanoparticles comprises silica nanoparticles.

6. The composition according to claim 5, wherein the silica nanoparticles have a D50 in the range of about 2 nm to about 150 nm.

7. The composition according to claim 1, wherein the plurality of nanoparticles are hydrophobically functionalized.

8. The composition according to claim 1, wherein at least most of the plurality of microparticles are substantially spherical in shape.

9. The composition according to claim 1, wherein the plurality of microparticles have a circularity of about 0.9 to about 1.

10. The composition according to claim 1, wherein the plurality of microparticles contain about 0.05 wt% to about 5 wt% of nanoparticles.

11. A composition comprising a plurality of microparticles containing polyvinyl alcohol and a plurality of hydrophobically functionalized silica nanoparticles, wherein the polyvinyl alcohol defines at least the outer surface of the microparticles, and at least most of the plurality of silica nanoparticles are disposed on the outer surface, The composition wherein the microparticles are substantially spherical, have an average size (D50) in the range of about 1 μm to about 150 μm, and have a geometric standard deviation (GSD) of about 3 or less.

12. Combining a water-soluble polymer and nanoparticles at a heating temperature equal to or higher than the melting point or softening temperature of the water-soluble polymer with a carrier fluid, wherein the water-soluble polymer and the carrier fluid are substantially immiscible at the heating temperature. Applying a shear force sufficient to disperse the water-soluble polymer as liquefied droplets in the carrier fluid at the heating temperature in the presence of the nanoparticles; After the liquefied droplets are formed, cooling the carrier fluid to a temperature at which at least solidified microparticles are formed, the microparticles comprising the water-soluble polymer and a plurality of the nanoparticles, the water-soluble polymer defining at least an outer surface of the microparticles, and at least a majority of the plurality of the nanoparticles being disposed on the outer surface, cooling; Cooling, wherein the microparticles are in the size range of about 20 μm to about 150 μm; Separating the microparticles from the carrier fluid, a method comprising.

13. The method according to claim 12, wherein the water-soluble polymer is selected from the group consisting of polyvinyl alcohol (PVA), polyethylene oxide (PEO), polyethylene glycol (PEG), poly(lactide-co-glycolide) (PLGA), and any combination thereof.

14. The method according to claim 12, wherein the water-soluble polymer comprises polyvinyl alcohol (PVA).

15. The method according to claim 12, wherein the plurality of nanoparticles comprises or consists essentially of a plurality of oxide nanoparticles, carbon black, or any combination thereof.

16. The method according to claim 12, wherein the plurality of nanoparticles comprises silica nanoparticles.

17. The method according to claim 16, wherein the silica nanoparticles have a D50 in the range of about 2 nm to about 150 nm.

18. The method according to claim 12, wherein the plurality of nanoparticles are hydrophobically functionalized.

19. The method according to claim 12, wherein at least a majority of the plurality of microparticles are substantially spherical in shape.

20. The method according to claim 12, wherein the plurality of microparticles comprises from about 0.05 wt% to about 5 wt% nanoparticles.

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