阅读说明：本技术 用于生产乳液的装置和方法 (Device and method for producing an emulsion ) 是由 劳尔·罗德里戈-戈麦斯 尤瑟夫·乔治·奥阿德 蒂莫西·罗伊·尼贾科夫斯基 加文·约翰·布罗德 于 2020-04-17 设计创作，主要内容包括：本发明涉及一种用于高通量生产具有低变异系数小滴/颗粒尺寸的乳液的装置和使用该装置的方法。该乳液形成装置包括外隔室(82)；分散相小滴形成设备；膜(140),该膜具有一个或多个孔、外表面积和内表面积、平均厚度,该膜设置在该外隔室与该分散相小滴形成设备之间；该膜的凸出指数为平均膜厚度的约(0.1)倍至约(10)倍。(The present invention relates to an apparatus for high throughput production of emulsions with low coefficient of variation droplet/particle sizes and methods of using the same. The emulsion forming device includes an outer compartment (82); a dispersed phase droplet forming device; a membrane (140) having one or more pores, an outer surface area and an inner surface area, an average thickness, the membrane disposed between the outer compartment and the dispersed phase droplet forming device; the film has a protrusion index of from about (0.1) to about (10) times the average film thickness.)

1. An emulsion forming device, comprising:

an outer compartment;

a dispersed phase droplet forming device;

a membrane having one or more pores, an outer surface area and an inner surface area, an average thickness, the membrane disposed between the outer compartment and the dispersed phase droplet forming device;

wherein the film has a bulge index of from about 0.1 to about 10 times the average film thickness.

2. The emulsion forming device of claim 1, wherein the membrane in combination with a membrane frame forms a membrane sheet.

3. The emulsion forming device of claim 2, wherein the total film external surface area of the one or more film sheets is about 400cm²To about 10cm²。

4. The emulsion forming device of claim 3, wherein the one or more membranes comprise one or more membrane segments having a membrane segment volume of about 100mm³To about 500mm³。

5. The emulsion forming device of claim 4, wherein the ratio of total membrane outer surface area to total membrane sheet segment volume is from about 0.5 to about 2.0, preferably from about 0.75 to about 1.5.

6. The emulsion forming device of claim 3, wherein the total membrane external surface area comprises one or more apertures forming an open area.

7. The emulsion forming device of claim 6, wherein the open area of the total film external surface area is from about 0.01% to about 20%.

8. The emulsion forming device of any of the preceding paragraphs, wherein the bulge is from about 0.2 times the average film thickness to about 5 times the average film thickness.

9. The emulsion forming device according to any of the preceding claims, wherein the film thickness is from about 1 μ ι η to about 1000 μ ι η.

10. The emulsion forming device of claims 2 to 9, wherein the film frame comprises one or more ribs forming one or more sections.

11. The emulsion forming device of claim 10, wherein the membrane frame comprises a membrane frame edge.

12. The emulsion forming device of claim 11, wherein the membrane is attached to the one or more ribs and the membrane frame edge.

13. The emulsion forming apparatus according to any one of the preceding claims, wherein the dispersed phase droplet forming device comprises one or more conduits having a feed inlet.

14. A method of producing an emulsion, the method comprising:

providing an emulsion forming device comprising:

an outer compartment;

a dispersed phase droplet forming device;

a membrane having one or more pores, an outer surface area and an inner surface area, an average thickness, the membrane disposed between the outer compartment and the dispersed phase droplet forming device; wherein the film has a bulge index of from about 0.1 times to about 10 times the average film thickness;

wherein the dispersed phase is in contact with the inner surface area of the membrane and the continuous phase is in contact with the outer surface area of the membrane;

pushing the dispersed phase into the continuous phase through the membrane pores, thereby forming an emulsion comprising a plurality of dispersed phase droplets in the continuous phase.

15. The method of claim 14, wherein the method produces droplets having a coefficient of variation on a volume percent basis ("CoV") of less than 50%.

Technical Field

The present invention relates to an apparatus and a method for producing an emulsion with droplets/particles with minimal size deviation and increased yield.

Background

Film emulsification is a process that produces an emulsion, foam or dispersion of one liquid phase (such as an oil) in a second immiscible liquid phase (such as water). The process typically employs shear at the membrane surface to detach the dispersed phase droplets from the membrane surface before they are dispersed in the immiscible continuous phase. In many cases, the droplets are subsequently solidified (e.g., via polymerization) to produce solid particles. Examples of such products include: calibration materials, food and flavor encapsulates, subcutaneous controlled release depot, ion exchange resins, and the like.

The size of the droplet depends on the imbalance of the following forces: detachment forces such as shear stress at the membrane surface, buoyancy, inertial forces, and the like; and cohesive forces such as interfacial tension and viscous forces. Emulsions having particles of substantially uniform size exhibit greater efficacy, thereby providing benefits not available from a broad particle size distribution. Where only certain particle sizes are required, a particle size distribution with minimal size deviation is desirable for various applications, such as the preparation of ion exchange resins, pre-heat treatment, phase change materials, surface softening chemistry, fragrance delivery, moisturizers, antiperspirant actives, or manufacturing processes involving molding or extrusion.

However, known processes comprising a dispersed phase and a continuous phase typically provide non-uniform droplets/particles over a relatively wide size range. Consequently, subsequent screening steps are necessary to provide particles in several more limited size ranges, which requires significant screening and storage costs, as well as rejection of the resulting commercially unusable particles.

Uniform droplets can be produced by various known devices including, for example, calibrated tubes or vibrating nozzles which must be adapted to the droplet size required in each case and are not particularly suitable for industrial manufacturing processes.

For industrial scale manufacturing of dispersed phase droplets or particles with small size deviations, a larger flux is required than the currently disclosed device process can provide. One way in which increased flux can be achieved is by increasing the size of the membrane, thereby increasing the number of pores. However, increasing the size (surface area) of the membrane results in a greater fluid pressure gradient across the membrane, resulting in increased particle size variation. The fluid pressure on the membrane will be greatest at the fluid entry point of the membrane and decrease as the fluid travels further away from the entry point.

The larger the membrane surface, the greater the likelihood of deformation and/or distortion of the membrane surface due to pressure applied to the dispersed phase to push it through the entire membrane; such deformation may result in "film bulging".

Such film bulging can cause the size of the droplets formed to change due to the difference in shear stress of the continuous phase flowing over the film bulging and the shear stress of the continuous phase flowing over a flat, non-bulged film. The resulting change in shear stress results in a change in droplet size. As the film bulge increases, the droplet detachment force becomes non-uniform, resulting in increased particle size variation or ultimately failure to emulsify under extreme conditions.

An attempt to increase flux was made by using a cylindrical membrane such as disclosed in US 9415530. However, cylindrical membranes as described in US 9415530 have a low surface area to volume ratio. The outer surface of the cylinder is where the membrane is located and the volume of the cylinder is used to distribute the dispersed phase liquid to the membrane. Thus, a low surface area to volume ratio may mean that the pressure drop created in the dispersed phase liquid will be higher, resulting in a pressure change of the dispersed phase along the membrane surface, thereby negatively affecting flux. Thus, cylindrical membranes cannot deliver high flux with low particle size variation due to the difficulty of uniformly distributing the fluid to the entire area of the membrane with the same pressure. With this geometry, a pressure gradient in the dispersed phase liquid will occur at different distances from the fluid entry point before reaching the back of the membrane. The pressure gradient difference may be higher than 10% resulting in droplet/particle size variation.

In view of the above, there is a need to produce particles of uniform size on an industrial scale.

Disclosure of Invention

Providing an emulsion forming device comprising: an outer compartment; a dispersed phase droplet forming device; a membrane having one or more pores, an outer surface area and an inner surface area, an average thickness, the membrane disposed between the outer compartment and the dispersed phase droplet forming device; wherein the film has a bulge index of from about 0.1 to about 10 times the average film thickness.

A method of producing an emulsion is provided, the method comprising providing an emulsion forming device having an outer compartment; a dispersed phase droplet forming device; a membrane having one or more pores, an outer surface area and an inner surface area, an average thickness, the membrane disposed between the outer compartment and the dispersed phase droplet forming device; wherein the film has a bulge index of from about 0.1 times to about 10 times the average film thickness; wherein the dispersed phase is in contact with the inner surface area of the membrane and the continuous phase is in contact with the outer surface area of the membrane; pushing the dispersed phase into the continuous phase through the membrane pores, thereby forming an emulsion comprising a plurality of dispersed phase droplets in the continuous phase.

Drawings

Fig. 1 shows a perspective view of a device according to some embodiments of the present invention.

Fig. 2 illustrates a cross-sectional view of a device according to some embodiments of the present invention along section line 2-2 as shown in fig. 1.

Fig. 3 illustrates a perspective view of a manifold according to some embodiments of the invention.

Fig. 4 illustrates a cross-sectional view of a manifold according to some embodiments of the present invention along section line 4-4 as shown in fig. 3.

Fig. 5 illustrates a perspective view of a membrane sheet and a membrane frame according to some embodiments of the invention.

Fig. 6 shows a microscopic image of a membrane according to some embodiments of the present invention.

Figure 7 shows a close-up microscopic image of a membrane according to some embodiments of the present invention.

FIG. 8 shows a cross-sectional view of a membrane pore according to one embodiment of the present invention.

Fig. 9 is a diagram of a membrane pore according to some embodiments of the invention.

Detailed Description

The present invention relates to one or more devices and methods of using such devices to produce emulsions having droplets with low coefficients of variation and high throughput. In certain aspects, the apparatus and methods as described herein overcome the deficiencies of the prior art by providing a larger membrane surface area as compared to prior art membranes, thereby allowing for increased emulsion production; while controlling the deformation (bulge) of the membrane and the pressure difference across the membrane, thereby facilitating the production of emulsion droplets having uniform size (low coefficient of variation).

As used herein, the word "or," when used as a conjunction with two or more elements, is intended to include the elements described individually or in combination; for example, X or Y, refers to X or Y or both.

As used herein, the articles "a" and "an" are understood to mean one or more of the materials claimed or described, for example, "oral care compositions" or "bleaching agents".

All percentages and ratios used below are by weight (wt%) of the total composition unless otherwise indicated. Unless otherwise indicated, all percentages, ratios, and levels of ingredients referred to herein are based on the actual amount of the ingredient and do not include solvents, fillers, or other materials with which the ingredient may be used in commercially available products.

All measurements referred to herein are made at about 23 ℃ (i.e., room temperature) unless otherwise indicated.

Surprisingly, by the practice of the present invention, exceptionally uniform droplets can be produced at high throughput. When the droplets comprise monomer, polymerization of the uniform droplets forms unexpectedly uniform particles. For example, in embodiments, the present invention provides spherical droplets having a volume average droplet diameter (i.e., an average diameter per volume based on a population of droplets) of between about 1 μm to about 250 μm. In some embodiments, a droplet has a substantially homogenous composition throughout its volume. In embodiments, the droplet may have a diameter greater than 1 μm. In embodiments, the droplets may have an average diameter (in a volume weighted distribution) of greater than 1 μm. In any of the preceding embodiments, the reference diameter may be greater than or equal to 1 μm, 2 μm, 3 μm, 4 μm, 5 μm, 10 μm, 15 μm, 20 μm, or 25 μm. In any of the preceding embodiments, the reference diameter may be about 1 μm to 100 μm, or 1 μm to 80 μm, or 1 μm to 65 μm, or 1 μm to 50 μm, or 5 μm to 80 μm, or 10 μm to 65 μm, or 15 μm to 65 μm, or 20 μm to 50 μm. For example, the reference diameter can be about 1 μm, 2 μm, 3 μm, 4 μm, 5 μm, 10 μm, 15 μm, 20 μm, 25 μm, 30 μm, 35 μm, 40 μm, 50 μm, 55 μm, 60 μm, 65 μm, 70 μm, 75 μm, 80 μm, 85 μm, 90 μm, 95 μm, or 100 μm. In embodiments, the droplet may have a diameter of greater than 1 μm, 2 μm, 3 μm, 4 μm, 5 μm, or 10 μm. In embodiments, a droplet may comprise a diameter of 1 μm to 80 μm, 3 μm to 80 μm, or 5 μm to 50 μm, or 10 μm to 50 μm. The volume average droplet diameter can be measured by any conventional method, for example, using optical imaging (dynamic or static), laser/light diffraction, extinction or electrical zone sensing or combinations thereof.

In another embodiment, the droplet is exceptionally homogeneous, having a volume percent based coefficient of variation ("CoV") of the droplet of less than 50%, or less than 45%, or less than 40%, or less than 35%, or less than 30%, or less than 25%, or less than 20%. For example, the droplet diameter CoV is from about 20% to about 50%, or from about 25% to about 40%, or from about 20% to about 45%, or from about 30% to about 40%, on a volume percent basis. The diameter, cov, (covv) based on volume percentage is calculated by the following equation:

wherein:

wherein:

σ_vstandard deviation of the volume distribution

μ_vDistribution mean of the volume distribution

d_iDiameter in fraction i

x_i,vFrequency in fraction i (corresponding to diameter i) of the volume distribution

In embodiments, a droplet may have a coefficient of variation in diameter on a number percentage basis of about 1% to about 150%, or about 1% to about 100%, or about 10% to about 80%, or about 10% to about 50%. For example, a droplet may have a coefficient of variation in diameter on a number percentage basis of about 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 60%, 70%, 80%, 90%, 100%, or 150%. The number population diameter coefficient of variation (CoVn) can be calculated by the following equation:

wherein:

wherein:

σ_nstandard deviation of the number distribution

μ_nDistribution mean of the number distribution

d_iDiameter in fraction i

x_i,nFrequency in the fraction i (corresponding to the diameter i) of the number distribution

The relationship between the number distribution and the volume distribution is represented by the following formula:

in embodiments, the invention can provide droplets having a narrow droplet size distribution, a coefficient of variation based on volume diameter of the droplets of about 20% to about 50%, and a dispersed phase flux of at least about 5 kg/h.

Fig. 1 and 2 show an embodiment of the present invention, including an emulsion forming device 10 that can be used to prepare droplets having a low droplet coefficient of variation and high throughput. As shown in fig. 2, apparatus 10 includes a dispersed phase input device, which in the illustrated embodiment is in the form of a dispersed phase feed conduit 14 that is in fluid communication with a source of the dispersed phase. The apparatus 10 also includes a continuous phase input for a continuous phase comprising a liquid immiscible with the dispersed phase, which in the illustrated embodiment is in the form of a continuous liquid supply conduit 18 in fluid communication with a source of the continuous phase.

Apparatus 10 includes a housing 80 forming an outer compartment 82 within which is disposed a dispersed phase droplet forming device, such as a manifold 100 having a diaphragm holder 102, where diaphragm holder 102 is used to hold one or more diaphragms 120 in fluid contact with the dispersed and continuous phases. The device achieves at least three main design considerations: 1) the mass must be kept to a minimum to keep the inertial load of the drive mechanism to a minimum; 2) the material forming the manifold must be compatible with the dispersed and continuous phases; and 3) ensuring laminar flow of the fluid in the outer compartment of the device to avoid shearing the emulsion.

The manifold may be made of any suitable material that is compatible with the dispersed phase, such asThe density is 1.4g/cm 3; polyoxymethylene, also known as acetal, polyacetal and polyoxymethylene (which are thermoplastic engineering plastics used in precision parts requiring high rigidity, low friction and excellent dimensional stability). Stainless steel is also contemplated.

To avoid turbulence and ensure laminar flow within the outer compartment 82, in embodiments, surfaces that are in a plane of movement substantially perpendicular to the flow of the dispersed phase through the membrane and that may be at least partially submerged in the continuous phase (such as the bottom edge of manifold 107) have been designed to reduce potential generation of turbulence; for example, as shown in FIG. 3, the bottom edge of manifold 107 has been beveled such that the surface is at most 45 to the plane of manifold 100. Other forms of turbulence reduction and laminar flow promotion, such as surface coatings, surface modifications, smooth or rounded surfaces, are contemplated within the scope of the present invention. Additionally, diaphragm 120 is mounted on diaphragm holder 102 of manifold 100, which is recessed into manifold outer surface 110 such that diaphragm outer surface 122 is substantially flush with manifold outer surface 110. By having the diaphragm outer surface 122 substantially flush with the manifold outer surface 110, it is ensured that laminar flow is maintained within the outer compartment 82 during emulsion formation, thereby helping to ensure consistent droplet formation.

Fig. 4 shows a cross section cut through the center of the manifold 100. Manifold 100 is divided into three separate zones 106A, 106B, and 106C, where three separate dispersed phases can be pumped to prepare an emulsion having multiple dispersed phases or a single dispersed phase. Each zone includes a gas inlet 130 in fluid communication with one or more dispersed phase feed conduits 14 to introduce a dispersed phase into manifold 100, one or more conduits 132, and one or more feed ports 114; although fig. 4 shows a single inlet 130 per zone, there may be more than one inlet, and each inlet may be connected to the manifold at a different point. The dispersed phase may flow from gas inlet 130 through or past manifold 100 via one or more conduits 132 that are fluidly connected to gas inlet 130 and dispersed phase feed conduit 14. Each zone 106A-106C is separated from another zone such that the dispersed phase provided to one zone is little or no mixed with the dispersed phase provided to another zone. One way to separate one zone from another is through the use of lateral drill plugs 112; however, other means of separation are also contemplated within the scope of the present invention, such as forming the conduits in a non-connected manner. A transverse drillplug 112 or any other conventional means may be used to prevent the dispersed phase from exiting at the edge of the manifold 116 and to prevent mixing between the zones 106A, 106B, and 106C. The only path for the dispersed phase is through the feed port 114 to the corresponding feed hole 124 in the membrane frame 160 as shown in fig. 5.

Referring to fig. 5, the membrane sheet 120 includes a membrane 140 and a membrane frame 160 that forms the boundary 123 and the segment 121 of the membrane sheet 120. The membrane frame 160 is sized to nest the membrane 140 such that the membrane 140 is in substantial contact with the membrane frame ribs 166 and the membrane frame edges 168. The membrane frame 160 also includes one or more feedholes 124, and may also include attachment devices 163 that allow the membrane sheet 120 to be removably or permanently connected to a manifold 100 surface, such as the sheet retainer 102. The membrane frame may be secured to the manifold sheet retainer 102 by any conventional means, such as threaded screws, rivets, or adhesives. Although fig. 2 and 3 show membrane 120 in a grid-like pattern, the membranes may be arranged along the manifold in any arrangement that allows for the production of desired droplets at a desired throughput.

Referring back to FIG. 5, the membrane frame 160 may be made of any suitable material, such as stainless steel orAnd is sized to contact the membrane around the membrane perimeter 144 (round/about)140 to provide a seal such that the dispersed phase provided to the membrane sheet 120 will not extrude from the membrane sheet 120 except through the membrane pores. The film frame 160 also includes a film frame edge 168 for nesting the film 140 and one or more raised areas or ribs 166, shown in horizontal and vertical orientations in this embodiment, forming a grid-like pattern that forms the membrane sections 121 when in contact with the film inner surface 146. Although a series of horizontal and vertical ribs 166 are shown in FIG. 5, the present invention is not limited to a grid-like pattern, as any useful orientation of the ribs is within the scope of the present invention. Furthermore, the width, shape and height of the ribs may vary along with their formation with the film forming sections. The size and dimensions of the segments may vary, but in embodiments the surface area of the segments, measured along the inner surface of the ribs forming the sides of the segments, may be about 400mm²To about 4mm²、350mm²To about 10mm²、300mm²To about 20mm²、250mm²To about 40mm²Or 200mm²To about 60mm². The rib height may be about 1mm to 5mm or about 2mm to 4 mm. The volume of the section can be about 100mm³To about 500mm³、150mm³To about 400mm³、200mm³To about 300mm³Within the range of (1). Further, in embodiments, the ratio of segment volume to membrane surface area may be from about 0.5 to about 2.0, from about 0.75 to about 1.5, or from about 0.9 to about 1.25.

The membrane may be attached to the membrane frame using any means known in the art, such as laser welding or adhesives. The membrane may have any suitable surface area, for example about 400cm²To about 10cm²About 350cm²To about 20cm²About 300cm²To about 40cm²About 250cm²To about 60cm²About 200cm²To about 80cm²About 150cm, from²To about 100cm². The attachment of the membrane perimeter 144 along the membrane frame edge 168 provides an airtight seal; in addition to the perimeter 144, the film is also attached along the ribs by any suitable means as described above. The attachment of the membrane to the frame along the perimeter and the ribs maintains the flatness of the membrane when subjected to trans-membrane pressure during operation. Film bulge failureShear stress and makes the shear stress non-uniform across the film. Non-uniform shear stress results in non-uniform droplet size. Membrane bulging is defined as the maximum normal deformation of the membrane from a static and non-prestressed state under transmembrane pressure. Film protrusion can be measured using the following method:

1. the membrane frame (160) is attached to the manifold (100) using screw fasteners such as M4 x 8mm long in four corners and tightened to a torque of 3.4 Nm. A spacing of 78mm between the centers of the manifolds of 90mm x 90mm will provide a load of 9.1kN that is sufficient to compress the O-ring seals to provide a seal between the manifolds and the membrane frame so as to reduce any potential leakage of compressed air between the manifolds and the membrane frame. The O-ring seal is made with a shore hardness of 70A to meet ASTM D2000, SAE J200 specifications.

The manifold was made of 6061 grade aluminum, with 1/8NPT 2 horizontal cross-drilled holes allowing compressed air to enter coincident with 4 vertical holes of 6mm diameter. The compressed air is supplied by a central internal supply or a small portable pump capable of providing a pressure of at least 1 bar to the side of the membrane attached to the membrane frame.

2. The centroid of each unsupported membrane area is identified. For example, if the unsupported area of the membrane is 1.5cm by 1.5cm, the centroid would be the intersection point of 75cm from one side and then 75cm from the edge perpendicular to the first edge.

3. The dial indicator plunger is placed directly above the centroid of the membrane area to be measured, where the plunger contacts the membrane surface at the centroid, but does not apply any pressure to the membrane. Wherein The Dial indicator is mounted to a spine frame that does not deflect due to The force of a spring inside The task-selected Dial indicator, such as a Starrett 653GJ Dial indicator with a granite base (The l.s. Starrett Company, atlol, MA).

4. The dial indicator is set to read zero.

5. A pressure of 1 bar was applied to the membrane.

6. Readings are taken from the dial indicator after a ten second delay to ensure inflation is complete. Readings are taken from the indicator while pressure is still being applied, which is the deflection resulting from the 1 bar pressure differential. This test was repeated for each section of the film. Each segment deflection must then be evaluated relative to the average thickness of the film, so for a 0.1mm film, if any index needs to be below the maximum, the bulge index (indicator reading) is between 0.1mm and 1 mm.

7. Determination of the bulge index-the measured deflection is divided by the average film thickness.

The thickness of the film can be measured by recording at least 5 separate measurements at different points of the film using a micrometer Mitutoyo 293-831-30(Mitutoyo USA co., Aurora, IL) or equivalent. During operation, the film's bulge index may range, for example, from about 0.1 to about 10 times the average film thickness or from about 0.2 to about 5 times, from about 0.3 to about 4.0 times, or from about 0.4 to about 3.5 times the average film thickness.

As shown in fig. 1 and 2, manifold 100 is connected to a device, such as a variable frequency/amplitude vibrator or oscillator 200, for displacing or vibrating the membrane perpendicular to the direction of flow of the dispersed phase through the membrane pores. As previously described, the dispersed phase is directed into the membrane 140 by pressure, such as a pulseless pump (i.e., syringe or gear pump), or under pressure from a pressurized dispersed phase tank through the feed orifice 124 to form a plurality of droplets. In some embodiments, the dispersed phase comprises a subsequently curable polymer precursor.

In embodiments, the shear force provided by the oscillatory motion is provided across the membrane at the point where the dispersed phase enters the continuous phase. In embodiments, the membrane may be mechanically moved in one or more directions. For example, the film may move harmonically along any line in the plane of the film. Without being bound by theory, the shear force is believed to interrupt the flow of the dispersed phase through the membrane, thereby creating droplets. In embodiments, the shear force may be provided by rapid displacement of the membrane by a vibratory, pulsed or oscillatory motion. In embodiments, the film may be moved in a direction perpendicular to the direction in which the dispersed phase exits the film.

In embodiments, the oscillation frequency of the present invention may range from about 5Hz to about 100Hz, or from about 10Hz to about 60 Hz. For example, the frequency may be about 5Hz, 10Hz, 15Hz, 20Hz, 25Hz, 30Hz, 35Hz, 40Hz, 45Hz, 50Hz, 60Hz, 70Hz, 80Hz, or 90 Hz. In embodiments, suitable values of movement amplitude are in the range of about 0.1mm to about 30mm, or about 1mm to about 20mm, or about 1mm to about 10 mm. For example, the amplitude of movement of the membrane may be about 0.1mm, 0.5mm, 1mm, 2mm, 3mm, 4mm, 5mm, 6mm, 7mm, 8mm, 9mm, 10mm, 15mm, 20mm, 25mm or 30 mm.

In an embodiment, the oscillating motion may be generated by means of a cam follower mounted offset from the axis of the main drive shaft (scotch yoke). This offset provides the oscillation amplitude, i.e. 1mm offset to 2mm displacement. The present invention allows displacement ranges of 0mm to about 40mm, about 2mm to about 40mm, or about 2mm to about 20 mm. When the shaft rotates, the yoke is constrained to move only in a plane at right angles to the axis of the drive shaft, along which it will move in an oscillating motion in time with the rotation of the main drive. The yoke and the cam follower are both designed to withstand the forces generated by the oscillations. The motion provided by the scotch yoke forms a simple harmonic curve, but modifying the servo drive to provide a cam system to the servo mechanism can produce any number of motion profiles, including trapezoidal profiles or polynomial profiles.

In an embodiment, a motor, such as an Allen Bradley MPL-B540 servomotor (Rockwell Automation, Milwaukee, Wis.), with a maximum speed of 4000rpm (oscillation frequency of 67Hz) and a maximum torque of 14.9NM may be used.

The membrane 140 in fig. 5 may be constructed of any material capable of having a plurality of pores suitable for injecting a liquid dispersed phase into a continuous phase. The membrane may be made of metal, ceramic material, silicon or silicon oxide, polymeric material, woven mesh material, or any combination thereof. A film comprising a metal may be used. In embodiments, the membrane is substantially metallic or entirely metallic. According to another embodiment, the membrane is a chemically resistant metal, such as nickel or steel. In yet another embodiment, the metal film is pretreated with a chemical agent (e.g., sodium hydroxide and/or an inorganic acid) to remove the surface oxide layer. In yet another embodiment, the membrane may be made of a non-metallic material, such as a membrane material-e.g. a membrane material

In yet another embodiment, the film may be made from a woven web material, such as a nylon woven web-e.g., Sefar(Sefar AG, Heiden, Switzerland). The pores of the membrane may originate from openings in the mesh material. The size and density of the openings in the mesh material is determined by the mesh size of the mesh. The mesh size is the number of openings per square inch of material. The open area (hole) is generally square or rectangular in shape and the size can vary depending on the fiber diameter. The approximate mesh and corresponding pore size are shown in table 1 below.

TABLE 1

Mesh net	Pore size (pore) -diameter (mum)
		400	23
500	19
		600	16
800	12
		1000	9
1200	6

Referring to fig. 6-8, in an embodiment, the membrane 140 has a plurality of pores 142. The pores may be of any suitable size, density, and arrangement on the outer surface 148 (the surface intended to face the continuous phase) or the inner surface 146 (the surface intended to face the dispersed phase) of the membrane. According to the invention, the hole density (number of holes/mm)²) May be determined by a variety of factors, such as the desired particle size, the desired droplet size, the chemistry of the monomer, the membrane material, the cross-sectional shape and length of the pores, the desired flux, the prevention of droplet coalescence, and the like. In embodiments, the pores on the membrane exterior surface 148 intended to face the outer compartment 82 may have an average diameter of about 0.1 μm to about 50 μm, or about 0.1 μm to about 35 μm, or about 0.5 μm to about 30 μm, or about 0.5 μm to about 20 μm, or about 1 μm to about 20 μm, about 4 μm to about 20 μm, or about 1 μm to about 10 μm. For example, the plurality of pores in the membrane can have an average diameter of about 0.1 μm, 0.5 μm, 1 μm, 2 μm, 3 μm, 4 μm, 5 μm, 6 μm, 7 μm, 8 μm, 9 μm, 10 μm, 15 μm, 20 μm, 25 μm, 30 μm, 35 μm, 40 μm, 45 μm, 50 μm. The plurality of pores may be randomly dispersed over the entire surface of the film, or may be arranged in a specified pattern across the surface of the film. For example, the membrane may include a plurality of apertures in a circular, rectangular, square, triangular, pentagonal, hexagonal, or octagonal array.

The membrane may have a pore density of about 10 pores/mm over its entire surface²To about 1000 holes/mm²About 15 holes/mm²To about 900 holes/mm²About 20 holes/mm²To about 800 holes/mm². The shape of the pores of the membrane may vary. For example, the shape of the hole may be cylindrical or conical. Generally, the pore size is a function of the film thickness such that the ratio of film thickness to pore size is in the range of 30:1, 20:1, or 15:1, depending on the type of material used for the film, the shape of the pores, and the technique used to form the pores. Fig. 8 is a schematic diagram illustrating a tapered membrane aperture 142 of the present invention.

Fig. 7 is a micrograph of a membrane 140 of the present invention. In this embodiment, the membrane is constructed of steel and contains a plurality of 7 μm pores 142.

The example film pattern shown in fig. 9 includes 5 μm aperture diameters, with a pitch between adjacent holes of 75 μm, as measured by the distance between the centers of adjacent holes. The example of fig. 9 shows a hexagonal array. Any suitable membrane may be used, including commercially available membranes. Table 2 below provides some example membrane characteristics that may be used in embodiments of the present disclosure.

TABLE 2

Pore diameter (d)p,μm)	Distance between holes (L, μm)	Open area (%)	L/dp *
				5	75	0.4	15
7	40	2.8	5.7
				4.64	75	0.35	16.2
2.5	40	0.35	16
				17.6	75	5	4.3
9.4	40	5	4.3

*L/d_pThe distance between the holes divided by the diameter of the holes

In fig. 9, the percent open area may be calculated as:

wherein the total area calculation is dependent on the shape of the membrane.

In embodiments, rectangular sections of the film may be used to calculate the percent open area, assuming the spacing and size of the holes through the remaining surface of the film are regular. In such embodiments, the cross-section of the holes within the rectangle is used, and the total area is represented by the area of the rectangle. Using fig. 9 as an example, the open area% can be calculated as follows:

open area (2 × hole section) 2 (pi/4) (d)_p) 77 μm [ where d_p＝7μm]

Total area (L) (L) ═ 75 μmx (√ 3 ═ L) (+) 130 μ ι η ═ 9750 μ ι η [ area of rectangle shown in fig. 9 ]

Open area% (% open area/total area) (% open area) (% total area)

In embodiments, adjacent ones of the plurality of pores in the membrane may be spaced apart by an average distance of about 5 μm to about 500 μm, or about 10 μm to about 250 μm, or about 10 μm to about 200 μm between the centers of each pore. For example, the plurality of pores in the membrane may have a distance between the center of each pore of about 5 μm, 10 μm, 20 μm, 30 μm, 40 μm, 50 μm, 60 μm, 70 μm, 75 μm, 80 μm, 90 μm, 100 μm, 110 μm, 120 μm, 130 μm, 140 μm, 150 μm, 160 μm, 170 μm, 180 μm, 190 μm, 200 μm, 210 μm, 220 μm, 230 μm, 240 μm, or 250 μm.

In embodiments, the open area of the membrane side facing the continuous phase may be from about 0.01% to about 20%, or from about 0.1% to about 10%, or from about 0.2% to about 10%, or from about 0.3% to about 5% of the surface area of the membrane side. For example, the open area of the membrane is about 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, or 8% of the surface area of the side surface of the membrane.

In embodiments, the dispersed phase may be about 1m³/m²h to about 500m³/m²h. Or about 1m³/m²h to about 300m³/m²h. Or about 2m³/m²h to about 200m³/m²h. Or about 5m³/m²h to about 150m³/m²h、5m³/m²h to about 100m³/m²h passes through a plurality of pores in the membrane. For example, the dispersed phase may be 1m³/m²h、2m³/m²h、3m³/m²h、4m³/m²h、5m³/m²h、6m³/m²h、7m³/m²h、8m³/m²h、9m³/m²h、10m³/m²h、20m³/m²h、30m³/m²h、40m³/m²h、50m³/m²h、60m³/m²h、70m³/m²h、80m³/m²h、90m³/m²h、100m³/m²h、150m³/m²h、200m³/m²h、250m³/m²h、300m³/m²h、350m³/m²h、400m³/m²h、450m³/m²h or 500m³/m²The flux rate of h passes through a plurality of pores in the membrane. As described herein, flux is calculated by the following equation:

where D is the diameter of the pores in the membrane.

The flow rate of the continuous phase may be adjusted in conjunction with the flow rate of the dispersed phase to obtain a desired concentration of the dispersed phase in the continuous phase.

It has been advantageously found that the concentration by weight of the dispersed phase in the continuous phase can be controlled based on the flow rate of the dispersed phase through the plurality of pores in the membrane and the flow rate of the continuous phase through the outer surface of the membrane. Advantageously, the methods of the present disclosure can allow for precise control of the concentration of the dispersed phase in the continuous phase. This may advantageously allow a high concentration of dispersed phase to be incorporated into the continuous phase while making the necessary controls to prevent overloading of the continuous phase and to avoid a concentration at which droplets of dispersed phase start to coalesce. In embodiments, the ratio of the continuous phase flow rate to the dispersed phase flow rate may be 0.1:1, 0.5:1, 1:1, 1.2:1, 1.5:1, 1.8:1, 2:1, 2.5:1, 3:1, 4:1, or 5: 1. As mentioned above, the choice of the stabilizer system may also allow to prevent or limit droplet coalescence while allowing a high concentration of the dispersed phase in the continuous phase. This is advantageous in order to obtain a high concentration of emulsion while maintaining a narrow particle size distribution.

According to embodiments, the concentration of the dispersed phase in the continuous phase may be from about 1% to about 70%, or from about 5% to about 60%, or from about 20% to about 60%, or from about 30% to about 60%, or from about 40% to about 60%. Advantageously, the processes herein can have a dispersed phase concentration in the continuous phase of about 30% or more, e.g., about 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, or 60%. In embodiments, the concentration of the dispersed phase in the continuous phase may be up to about 60% while maintaining limited coalescence such that the number population diameter CoV in the emulsion is less than or equal to 100%. In embodiments, the resulting emulsion may have a dispersed phase concentration in the continuous phase of greater than or equal to 40% or greater than or equal to 50% while maintaining a number population diameter CoV in the emulsion of less than or equal to 100%. In embodiments, a high concentration of the dispersed phase in the continuous phase may be obtained by having: (1) high flux of the dispersed phase through the membrane, (2) tuned stabilizer systems, and (3) high shear stress on the membrane surface.

Having a high flux of the dispersed phase in the membrane may be advantageous to obtain a high concentration of the dispersed phase in the continuous phase, because the higher the velocity of the dispersed phase, the more the dispersed phase reaches the surface of the membrane, the more the amount of oil emulsified, and thus the higher the total concentration of the dispersed phase in the continuous phase. Having a tuned stabilizer system can be advantageous because the stabilizer system can stabilize droplets of the dispersed phase and reduce the rate of coalescence of the dispersed phase droplets and increase the rate of mass transfer. Increasing the mass transfer rate may be advantageous to avoid coalescence and achieve a narrow size distribution, since the new molecules of the stabilizer system must reach the surface of the film at the same time as they are formed. Increasing the mass transfer rate can help transport the dispersed phase droplets away from the surface of the film where new droplets are formed, in order to avoid further coalescence and reduce the local concentration of the dispersed phase in the vicinity of the film. However, having a high concentration of the stabilizer system in the emulsion increases the viscosity of the emulsion. Having an increased emulsion viscosity may slow the mass transfer of the stabilizer molecules and the dispersed phase through the continuous phase, resulting in a higher rate of coalescence of the dispersed phase. Thus, the stabilizer system needs to be tuned to have sufficient concentration in the emulsion to achieve advantage without negatively impacting the emulsion by increasing viscosity too much. Having high shear stress at the film surface may be advantageous because increased shear stress reduces the droplet size of the dispersed phase, which facilitates movement of the droplets of the dispersed phase from the film surface.

In embodiments, table 3 shows the minimum and maximum values related to the concentration of the dispersed phase in the continuous phase. τ can be calculated using the following equation:

wherein:

τ_maxis the peak shear event (maximum shear stress) during oscillation

Rho-density of continuous phase

Viscosity of the mu-continuous phase

a-amplitude of oscillation

f-oscillation frequency

TABLE 3

The membrane pores may be made by any conventional method. For example, the film holes may be made by drilling the film, laser processing, electroforming, or water jet (water peening). The film holes are preferably electroformed by electroplating or electroless nickel plating on a suitable mandrel. In another embodiment, the pores of the membrane are perpendicular to the surface. In another embodiment, the membrane pores are positioned at an angle, preferably at an angle of 40 ° to 50 °. In embodiments, the overall average thickness of the membrane is in the range of from about 1 μm to about 1000 μm, or from about 5 μm to about 500 μm, or from about 10 μm to about 500 μm, or from about 20 μm to about 200 μm. For example, the thickness of the film can be about 10 μm, 15 μm, 20 μm, 25 μm, 30 μm, 40 μm, 50 μm, 60 μm, 70 μm, 80 μm, 90 μm, 100 μm, 110 μm, 120 μm, 130 μm, 140 μm, 150 μm, or 200 μm.

In certain embodiments, the particles described herein can be capsules in that they have a polymeric shell surrounding a core. Capsules according to embodiments of the present disclosure may include a benefit agent. In embodiments, the capsule may be incorporated into a formulated product to release the benefit agent upon rupture of the capsule. Various formulated products having capsules are known in the art, and capsules according to the present disclosure may be used in any such product. Examples include, but are not limited to, laundry detergents, hand soaps, cleaning products, lotions, fabric enhancers, beauty care products, skin care products, and other cosmetic products.

In various embodiments, capsules with a narrow particle size distribution are produced. In various embodiments, the capsules have a percent delta burst strength of 15% to 230% (as discussed in more detail below) and a shell thickness of about 20nm to about 400 nm. In various embodiments, the capsules can have an average diameter greater than 1 μm. In embodiments, each capsule has a diameter greater than 1 μm. In various embodiments, the capsules have a coefficient of variation in diameter (in number%) between 10% and 100% and an average ratio of volume percent of core material to volume percent of shell material that is greater than or equal to about 95: 5. In embodiments, the capsules have an average shell thickness of 20nm to 300 nm. In embodiments, the capsules have a ratio of the average volume percent of core material to the average volume percent of shell material of greater than about 95: 5.

In embodiments, the population of capsules may comprise a percent delta burst strength in the range of about 15% to about 230% and a shell thickness of 20nm to 400 nm. In embodiments, a population of capsules can include a number population coefficient of variation of diameter from 10% to 100%, a shell thickness from 20nm to 400nm, and an average volume percent ratio of core material to shell material based on the total volume of the capsules of greater than or equal to about 90: 10.

The foregoing represents exemplary embodiments of combinations of capsule characteristics. These and various additional features are described in further detail below. It should be understood herein that other combinations of such features are contemplated herein, and may be any one or more of such features described in the following paragraphs that may be used in various combinations.

In various embodiments, the capsules are provided as a single capsule, a portion of a population of capsules, or a portion of any suitable number of multiple capsules. References herein to individual capsule characteristics, parameters and characteristics are to be understood as applicable to a plurality of capsules or groups of capsules. It should be understood that such features and associated values may be an average or mean of a plurality of capsules or capsule populations unless otherwise indicated herein.

In any of the embodiments herein, the core may comprise a benefit agent. In various embodiments, the core may be a liquid.

In embodiments, the capsule or population of capsules may have an average volume percent ratio of core material to shell material based on the total volume of the capsule of at least 80 to 20, 85 to 15, 90 to 10, 95 to 5, 98 to 2, 99 to 1, 99.9 to 0.1, or 99.99 to 0.01. For example, a capsule or population of capsules may have an average volume percent ratio of core material to shell material based on the total volume of the capsule of 80 to 20, 85 to 15, 90 to 10, 95 to 5, 98 to 2, 99 to 1, 99.9 to 0.1, or 99.99 to 0.01. In embodiments, the population of capsules may have an average volume percent ratio of core material to shell material based on the total volume of the capsules of from about 80 to 20 to about 99.9 to 0.1, or from about 90 to 10 to about 99.9 to 0.1, or from about 95 to 5 to about 99.99 to 0.01, or from about 98 to 2 to about 99.99 to 0.01. In embodiments, the entire population of capsules may have an average volume percent ratio of core material to shell material based on the total volume of the capsules of at least 80 to 20, or at least 90 to 10, or at least 95 to 5, or at least 98 to 2. High core-shell material ratios can advantageously produce high efficiency capsules with high levels of benefit agent per capsule. In embodiments, this may allow for a high loading of benefit agent in a formulated product with capsules and/or allow for a smaller amount of capsules to be used in the formulated product.

In embodiments, the capsule or population of capsules may have a percent delta burst strength of from about 10% to about 500%, or from about 10% to about 350%, or from about 10% to about 230%, from about 15% to about 350%, from about 15% to about 230%, from about 50% to about 350%, from about 50% to about 230%, from about 15% to about 200%, from about 30% to about 200%. For example, a population of capsules may have a percentage delta burst strength of about 10%, 15%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 110%, 120%, 130%, 140%, 150%, 160%, 170%, 180%, 190%, 200%, 210%, 220%, 230%, 240%, 250%, 300%, 350%, 400%, or 500%. Percent delta burst strength can be calculated using the following formula:

wherein FS represents the rupture strength andand FS at d_iIs the FS of the capsule at percentile "i" of the volume size distribution. The burst strength can be measured by the burst strength test method described further below.

A percent delta burst strength in the range of 15% to 230% can be beneficial to ensure that the capsules properly and more uniformly release the benefit agent in the formulated product at the desired time. For example, in embodiments, the formulated product may be a laundry detergent, and capsules having a percent delta burst strength in the range of 15% to 230% may beneficially ensure that substantially all of the capsules release the benefit agent at the targeted stage of the wash cycle.

In embodiments, the capsules may have a diameter greater than 1 μm. In embodiments, the capsules or population of capsules may have an average diameter greater than 1 μm. In embodiments, the capsules or population of capsules may have a median diameter greater than 1 μm. In any of the preceding embodiments, the reference diameter may be greater than or equal to 1 μm, 2 μm, 3 μm, 4 μm, 5 μm, 10 μm, 15 μm, 20 μm, or 25 μm. In any of the preceding embodiments, the reference diameter may be about 1 μm to 100 μm, or 1 μm to 80 μm, or 1 μm to 65 μm, or 1 μm to 50 μm, or 5 μm to 80 μm, or 10 μm to 65 μm, or 15 μm to 65 μm, or 20 μm to 50 μm. For example, the reference diameter can be about 1 μm, 2 μm, 3 μm, 4 μm, 5 μm, 10 μm, 15 μm, 20 μm, 25 μm, 30 μm, 35 μm, 40 μm, 50 μm, 55 μm, 60 μm, 65 μm, 70 μm, 75 μm, 80 μm, 85 μm, 90 μm, 95 μm, or 100 μm. In embodiments, the entire population of capsules may have a diameter greater than 1 μm, 2 μm, 3 μm, 4 μm, 5 μm, or 10 μm. In embodiments, the entire population of capsules may comprise a diameter of 1 μm to 80 μm, 3 μm to 80 μm, or 5 μm to 50 μm, or 10 μm to 50 μm.

In embodiments, the capsule may have a coefficient of variation in diameter on a volume percent basis of less than 50%, or less than 45%, or less than 40%, or less than 35%, or less than 30%, or less than 25%, or less than 20%. For example, the diameter CoV is from about 20% to about 50%, or from about 25% to about 40%, or from about 20% to about 45%, or from about 30% to about 40%, on a volume percent basis. The diameter, cov, (covv) based on volume percentage is calculated by the following equation:

wherein the content of the first and second substances,

the formula is termed as follows:

σ_vstandard deviation of the volume distribution

μ_vDistribution mean of the volume distribution

d_iDiameter in fraction i: (>1μm)

x_i,vFrequency in fraction i (corresponding to diameter i) of the volume distribution

In embodiments, the capsules may have a coefficient of diameter variation on a number percentage basis of from about 1% to about 150%, or from about 1% to about 100%, or from about 10% to about 80%, or from about 10% to about 50%. For example, a capsule may have a number percentage based diameter coefficient change of about 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 60%, 70%, 80%, 90%, 100%, or 150%. The number population diameter coefficient of variation (CoVn) can be calculated by the following equation:

wherein:

wherein:

σ_nstandard deviation of the number distribution

μ_nDistribution mean of the number distribution

d_iDiameter in fraction i: (>1μm)

x_i,nFrequency in the fraction i (corresponding to the diameter i) of the number distribution

The relationship between the number distribution and the volume distribution is represented by the following formula:

core

In any of the embodiments disclosed herein, the capsule may comprise a benefit agent in the core. In embodiments, the benefit agent may include one or more perfumes, brighteners, insect repellents, silicones, waxes, flavors, vitamins, fabric softeners, skin care agents, UV blockers, enzymes, probiotics, dye polymer conjugates, dye clay conjugates, perfume delivery systems, sensates, cooling agents, insect attractants, pheromones, antimicrobials, dyes, pigments, bleaches, and disinfectants. In embodiments, the benefit agent may comprise a perfume or a perfume delivery system.

In embodiments, the benefit agent may be present in an amount of about 45 wt% or more based on the total weight of the core. In embodiments, the benefit agent is a perfume or perfume delivery system, and in embodiments, the perfume is present in an amount of about 45 wt% or more based on the total weight of the core. In embodiments, the capsule may comprise about 45 wt% or more, or 50 wt% or more, or 60 wt% or more, or 70 wt% or more, or 80 wt% or more, or 90 wt% or more of the benefit agent, based on the total weight of the core.

In embodiments, the benefit agent may have a ClogP value greater than or equal to 1. In embodiments, the benefit agent may have a ClogP value of 1 to 5, or 1 to 4, or 1 to 3, or 1 to 2. For example, the benefit agent may have a ClogP value of about 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, or 5.

In embodiments, the core may further comprise additional components, such as excipients, carriers, diluents, and other agents. In embodiments, the benefit agent may be mixed with an oil. Non-limiting examples of oils include isopropyl myristate, C₄-C₂₄Mono-, di-, and tri-esters of fatty acids, castor oil, mineral oil, soybean oil, hexadecanoic acid, methyl ester isododecane, isoparaffinic oils, polydimethylsiloxane, brominated vegetable oils, and combinations thereof. The capsules may also have different ratios of oil to benefit agent in order to produce different populations of microcapsules that may have different bloom patterns. Such populations may also incorporate different flavor oils in order to prepare populations of capsules exhibiting different bloom patterns and different flavor experiences. US 2011-0268802 discloses other non-limiting examples of oils and is hereby incorporated by reference. In embodiments, the oil mixed with the benefit agent may include isopropyl myristate.

Shell

In any of the embodiments disclosed herein, the capsule shell can be a polymeric shell, and can comprise greater than 90% polymeric material, or greater than 95% polymeric material, or greater than 98% polymeric material, or greater than 99% polymeric material. In embodiments, the polymeric shell may comprise one or more of a homopolymer, a copolymer, and a crosslinked polymer. In embodiments, the polymeric shell may comprise a copolymer and a cross-linked polymer. In embodiments, the polymeric shell may be made by simple and/or complex coacervation. In embodiments, the polymeric shell may comprise one or more of a polyacrylate, polymethacrylate, melamine formaldehyde, polyurea, polyurethane, polyamide, polyvinyl alcohol, chitosan, gelatin, polysaccharide, or gum. In embodiments, the polymeric shell comprises a poly (meth) acrylate. As used herein, the term "poly (meth) acrylate" may be a polyacrylate, a polymethacrylate, or a combination thereof.

In embodiments, the capsule may have a shell thickness or average shell thickness of from about 1nm to about 1000nm, or from about 1nm to about 800nm, or from about 1nm to about 500nm, or from about 5nm to about 400nm, or from about 10nm to about 500nm, or from about 10nm to about 400nm, or from about 20nm to about 500nm, or from about 20nm to about 400nm, or from about 50nm to about 350 nm. For example, the shell thickness or average shell thickness can be about 1nm, 5nm, 10nm, 20nm, 30nm, 40nm, 50nm, 60nm, 70nm, 80nm, 90nm, 100nm, 150nm, 200nm, 250nm, 300nm, 350nm, 400nm, 450nm, 500nm, 600nm, 700nm, 800nm, 900nm, or 1000 nm. In embodiments, the entire population of capsules may have a shell thickness of less than 1000nm, or less than 800nm, or less than 600nm, or less than 400nm, or less than 350 nm.

In various embodiments, the capsules and methods of making capsules allow for reduced shell thicknesses. For example, the capsule may have a thickness of about 20nm to about 400 nm. In various embodiments, capsules having a shell thickness of about 20nm to about 400nm may maintain sufficient burst strength and a desired release profile to maintain functionality of the formulated product. For example, in such embodiments, the capsule can have a median rupture strength of from about 1MPa to about 14 MPa. In such embodiments, the reduced shell thickness may advantageously allow for a reduced amount of desired polymer precursor material compared to conventional capsules, which may reduce cost and may reduce environmental impact.

In embodiments, the capsule may have a delta burst strength of from about 15% to about 230% and a shell thickness of from about 20nm to about 400 nm. Such combinations may be advantageous, allowing for uniform and timely release in the formulated product while reducing the polymer material required.

In embodiments, the capsule may have a coefficient of variation in diameter, measured as a number percentage, of about 10% to about 100%, an average shell thickness in a range of about 20nm to about 400nm, and an average volume percent ratio of core material to shell material based on the total volume of the capsule of greater than or equal to about 95 to 5.

Preparation method

According to embodiments, a method of making a capsule having a core surrounded by a polymeric shell may comprise emulsifying using a membrane. In various embodiments, the method of making the capsule may comprise dispersing droplets of the dispersed phase in the continuous phase by passing the dispersed phase through a plurality of pores in the film. In embodiments, the method may include passing the dispersed phase through the membrane from the inner surface of the membrane to the outer surface of the membrane into the continuous phase flowing over the outer surface of the membrane. Upon exiting the plurality of pores on the outer surface of the film, the dispersed phase forms as droplets of the dispersed phase. In embodiments, the membrane may be mechanically moved while the dispersed phase passes through the membrane to create shear forces on the outer surface of the membrane to exit the membrane and disperse into the flowing continuous phase.

In embodiments, the dispersed phase may comprise a polymer precursor and a benefit agent. In embodiments, the method can further comprise subjecting the dispersed phase emulsion in the continuous phase to conditions sufficient to initiate polymerization of the polymer precursor within the droplets of the dispersed phase. For the particular polymer precursor present in the dispersed phase, suitable polymerization conditions can be selected as known in the art. Without intending to be bound by theory, it is believed that upon initiation of polymerization, the polymer becomes insoluble in the dispersed phase and migrates within the droplet to the interface between the dispersed phase and the continuous phase, thereby defining the capsule shell.

In embodiments, the process may form capsules using an inside-outside polymerization process in which the dispersed phase droplets comprise a soluble polymer precursor that becomes insoluble \ migrates to the interface between the dispersed and continuous phases after polymerization, thereby forming capsule shells around the core that comprise the remaining components of the dispersed phase, such as the benefit agent, after complete polymerization.

In embodiments, the dispersed phase may comprise one or more of a polymer precursor, an anti-solvent, and a benefit agent. In embodiments, the polymer precursor may include one or more monomers and oligomers, including mixtures of monomers and oligomers. In embodiments, the polymer precursor is soluble in the dispersed phase. In embodiments, the polymer precursor is multifunctional. As used herein, the term "multifunctional" refers to having more than one reactive chemical functional group. For example, the reactive chemical functional group F may be a carbon-carbon double bond (i.e., an ethylenically unsaturated group) or a carboxylic acid. In embodiments, the polymer precursor may have any desired number of functional groups F. For example, the polymer precursor may comprise two, three, four, five, six, seven, eight, nine, ten, eleven, or twelve functional groups F).

In embodiments, the polymer precursor may include an ethylenically unsaturated monomer or precursor. In embodiments, the polymer precursor may comprise an amine monomer selected from the group consisting of: aminoalkyl acrylates, alkylaminoalkyl acrylates, dialkylaminoalkyl acrylates, aminoalkyl methacrylates, alkylaminoalkyl methacrylates, dialkylaminoalkyl methacrylates, t-butylaminoethyl methacrylate, diethylaminoethyl methacrylate, dimethylaminoethyl methacrylate, dipropylaminoethyl methacrylate, and mixtures thereof; and a plurality of multifunctional monomers or multifunctional oligomers. In embodiments, the polymer precursor may include one or more acrylates. For example, the polymer precursor may include one or more of methacrylate, ethyl acrylate, propyl acrylate, and butyl acrylate. In embodiments, the polymer precursor is one or more ethylenically unsaturated monomers or oligomers. In various embodiments, the ethylenically unsaturated monomer or oligomer is multifunctional. In embodiments, the multifunctional ethylenically unsaturated monomer or oligomer is a multifunctional ethylenically unsaturated (meth) acrylate monomer or oligomer. In embodiments, the multifunctional ethylenically unsaturated monomer or oligomer may comprise two, three, four, five, six, seven, eight, nine, ten, eleven, or twelve functional groups F. In embodiments, the multifunctional ethylenically unsaturated monomer or oligomer may comprise at least three functional groups. In embodiments, the multifunctional ethylenically unsaturated monomer or oligomer may comprise at least four functional groups. In embodiments, the multifunctional ethylenically unsaturated monomer or oligomer may comprise at least five functional groups.

These oligomeric materials with multiple functional groups are capable of crosslinking the polymer backbone, allowing the formation of a shell wall by insolubility and polymer precipitation at the oil-water interface. Crosslinking also provides rigidity and durability to the shell wall. In embodiments, the polymer precursor may comprise one or more of polyacrylates, acrylates, polymethacrylates, methacrylates, melamine formaldehyde, polyureas, ureas, polyurethanes, polyamides, amides, polyvinyl alcohols, chitosan, gelatin, polysaccharides, and gums. In embodiments, the polymer precursor may comprise a polyacrylate precursor. In embodiments, the polymer precursor may comprise a polyacrylate or polymethacrylate precursor having at least three functional groups. For example, the polymer precursor may be a compound of formula I.

In embodiments, the polymer precursor may include one or more of a hexafunctional aromatic urethane acrylate oligomer, t-butylaminoethyl methacrylate, 2-carboxyethyl acrylate, pentaerythritol triacrylate, pentaerythritol tetraacrylate, ditrimethylolpropane tetraacrylate, propoxylated trimethylpropane triacrylate, dipentaerythritol pentaacrylate, tris (2-hydroxyethyl) isocyanurate triacrylate.

In embodiments, the polymer precursor may be present in the dispersed phase in an amount of from about 0.01 wt% to about 30 wt%, based on the total weight of the dispersed phase, or from about 0.01 wt% to about 20 wt%, or from about 0.05 wt% to about 20 wt%, or from about 0.1 wt% to about 15 wt%, or from about 0.5 wt% to about 15 wt%, or from about 1 wt% to about 15 wt%, or from about 5 wt% to about 15 wt%, or from about 0.05 wt% to about 15 wt%, based on the total weight of the dispersed phase. For example, the polymer precursor can be present in an amount of about 0.01, 0.05, 0.1, 0.5, 1,2, 3, 4, 5, 6, 7, 8, 9,10, 11, 12, 13, 14, or 15 weight percent based on the total weight of the dispersed phase.

In embodiments, the continuous phase may be free or substantially free of polymer precursors. As used herein, the term "substantially free of polymer precursors" means that the continuous phase comprises 0.0001 wt% or less of polymer precursors.

In embodiments, the polymer precursors contained in the dispersed phase polymerize to form about 98% or more by weight of the polymer comprising the shell. In embodiments, the shell may comprise about 99% by weight or more of the polymer polymerized from the polymer precursor derived from the dispersed phase. In embodiments, the shell may comprise about 99.9% by weight or more of the polymer polymerized from the polymer precursor derived from the dispersed phase.

In embodiments, the method of making the capsules may include a stabilizer system in one or both of the dispersed and continuous phases. In embodiments, the stabilizer system may be present in an amount of about 0.01 wt% to about 30 wt%, based on the total weight of the continuous phase, or in an amount of about 0.1 wt% to about 25 wt%, or about 0.5 wt% to about 20 wt%, or about 1 wt% to about 20 wt%, or about 0.5 wt% to about 10 wt%, based on the total weight of the continuous phase. For example, the stabilizer system may be present in an amount of about 0.1, 0.2, 0.3, 0.4, 0.5, 1,2, 3, 4, 5, 6, 7, 8, 9, or 10 weight percent.

In embodiments, the stabilizer system may comprise a primary stabilizer present in the continuous phase. In embodiments, the primary stabilizer may be present in an amount of from about 51 wt% to about 100 wt%, based on the total weight of the stabilizer system. In embodiments, the primary stabilizer may include an amphiphilic nonionic stabilizer that is soluble or dispersible in the continuous phase. In embodiments, the primary stabilizer may include one or more of the following: polysaccharides, pyrrolidone-based polymers, natural source gums, polyalkylene glycol ethers; alkylphenol, condensation products of aliphatic alcohols or fatty acids with alkylene oxides, ethoxylated alkylphenol, ethoxylated arylphenol, ethoxylated polyarylphenol, carboxylic esters solubilized with polyols, polyvinyl alcohol, polyvinyl acetate, copolymers of polyvinyl alcohol and polyvinyl acetate, polyacrylamide, poly (N-isopropylacrylamide), poly (hydroxypropyl 2-methacrylate), poly (2-ethyl-2-oxazoline), poly (2-isopropenyl-2-oxazoline-co-methyl methacrylate), poly (methyl vinyl ether), polyvinyl alcohol-co-ethylene, and acetate modified polyvinyl alcohol. In embodiments, the primary stabilizer may include polyvinyl alcohol. In embodiments, the polyvinyl alcohol may have a degree of hydrolysis of 50% to 99.9%. In embodiments, the polyvinyl alcohol may have a degree of hydrolysis of less than 95%. In embodiments, the polyvinyl alcohol may have a degree of hydrolysis of 50% to 95%, or 60% to 95%, or 70% to 95%, or 75% to 95%. For example, the degree of hydrolysis may be 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%. In embodiments, the polyvinyl alcohol can have a viscosity of 1cP to 100 cP. Preferably 10 cP. In embodiments, the polyvinyl alcohol may have a molecular weight from X to Y.

In embodiments, selection of a stabilizing system as described herein may advantageously help to stabilize droplets at the surface of the film, which in turn may provide more uniform droplet size, as well as low coefficient of variation or particle size, low percent delta rupture strength. In embodiments, a primary stabilizer, such as polyvinyl alcohol, may be used to stabilize the emulsion at the interface between the dispersed phase droplets and the continuous phase, and to help prevent or reduce droplet coalescence. In embodiments, the stabilizer system may help provide an emulsion with a droplet size having a coefficient of variation in diameter of less than or equal to 40%.

In embodiments, the stabilizer system further comprises one or more minor amounts of a stabilizer. In embodiments, the stabilizer system includes a micro-stabilizer in an amount of from about 49 wt% to about 0.1 wt%, based on the total weight of the stabilizer system. For example, the minor stabilizer may be present in an amount of 1%, 2%, 3%, 4%, 5%, 10%, 20%, 30%, 40%, or 50% of the total weight of the stabilizer system. In embodiments, the minor stabilizer may comprise a minor amount of a protective colloid present in the continuous phase. In embodiments, the minor amount of protective colloid may include one or more of a low molecular weight surfactant, a cationic stabilizer, and an anionic stabilizer. In embodiments, the micro-stabilizer may include a low molecular weight surfactant, wherein the low molecular weight surfactant may include one or more short chain EO/PO and alkyl sulfates.

The method further comprises initiating polymerization of the monomer within the droplets of the dispersed phase. Various initiation methods can be used as known in the art and selected based on the monomers to be polymerized. By way of example, initiating polymerization of the monomer may include methods involving one or more of free radical, pyrolysis, photolysis, redox reactions, persulfates, ionizing radiation, electrolysis, or ultrasonic treatment. In embodiments, initiating polymerization of the polymer precursor may include heating a dispersion of dispersed phase droplets in a continuous phase. In embodiments, initiating polymerization of the monomer may include exposing the dispersion of dispersed phase droplets in the continuous phase to ultraviolet radiation. In embodiments, initiating polymerization may include activating an initiator present in one or both of the dispersed phase and the continuous phase. In embodiments, the initiator may be one or more of a thermally activated initiator, a photo-activated initiator, a redox activated initiator, and an electrochemically activated initiator.

In embodiments, the initiator may comprise a free radical initiator, wherein the free radical initiator may be one or more of a peroxy initiator, an azo initiator, a peroxide, and a compound such as 2,2' -azobismethylbutyronitrile, dibenzoyl peroxide, and the like. More specifically and without limitation, the radical initiator may be selected from the group of initiators comprising: azo or peroxy initiators, such as peroxides, dialkyl peroxides, alkyl peroxides, peroxy esters, peroxy carbonates, peroxy ketones and peroxy dicarbonates, 2 '-azobis (isobutyronitrile), 2' -azobis (2, 4-dimethylvaleronitrile), 2 '-azobis (2-methylpropionitrile), 2' -azobis (methylbutyronitrile), 1 '-azobis (cyclohexanecarbonitrile), 1' -azobis (cyanocyclohexane), benzoyl peroxide, decanoyl peroxide; lauroyl peroxide; benzoyl peroxide, di (n-propyl) peroxydicarbonate, di (sec-butyl) peroxydicarbonate, di (2-ethylhexyl) peroxydicarbonate, 1-dimethyl-3-hydroxybutyl peroxyneodecanoate, a-cumyl peroxyneoheptanoate, tert-amyl peroxyneodecanoate, tert-butyl peroxyneodecanoate, tert-amyl peroxypivalate, tert-butyl peroxypivalate, 2, 5-dimethyl-2, 5-di (2-ethylhexanoylperoxy) hexane, tert-amyl peroxy-2-ethylhexanoate, tert-butyl peroxyacetate, di-tert-amyl peroxyacetate, tert-butyl peroxide, di-tert-amyl peroxide, 2, 5-dimethyl-2, 5-di- (tert-butylperoxy) -3-hexyne, Cumene hydroperoxide, 1-di- (tert-butylperoxy) -3,3, 5-trimethyl-cyclohexane, 1-di- (tert-butylperoxy) -cyclohexane, 1-di- (tert-pentylperoxy) -cyclohexane, ethyl-3, 3-di- (tert-butylperoxy) -butyrate, tert-amyl perbenzoate, tert-butyl perbenzoate, ethyl-3, 3-di- (tert-pentylperoxy) -butyrate, and the like.

In embodiments, the initiator may comprise a thermal initiator. In embodiments, the thermal initiator may have a bond dissociation energy in the range of 100kJ/mol to 170 kJ/mol. The thermal initiator may comprise one or more of the following: peroxides such as acyl peroxide, acetyl peroxide, and benzoyl peroxide; azo compounds such as 2,2 '-azobisisobutyronitrile, 2' -azobis (2, 4-dimethylvaleronitrile), 4 '-azobis (4-cyanovaleric acid) and 1,1' -azobis (cyclohexanecarbonitrile); and disulfides.

In embodiments, the initiator may comprise a redox initiator, such as a combination of an inorganic reducing agent and an inorganic oxidizing agent. For example, reducing agents such as peroxodisulfates, HSO₃ ^-、SO₃ ^2-、S-₂O₃ ^2-、S₂O₅ ^2-Or alcohols having a source of oxidant, such as Fe²⁺、Ag⁺、Cu²⁺、Fe³⁺、ClO₃ ^-、H₂O₂、Ce⁴⁺、V⁵⁺、Cr⁶⁺Or Mn³⁺。

In embodiments, the initiator may include one or more photochemical initiators, such as benzophenone; acetophenone; benzil; benzaldehyde; o-chlorobenzaldehyde; xanthone; a thioxanthone; 9, 10-anthraquinone; 1-hydroxycyclohexyl phenyl ketone; 2, 2-diethoxyacetophenone; dimethoxy phenylacetophenone; methyldiethanolamine; dimethylaminobenzoic acid salt; 2-hydroxy-2-methyl-1-phenylpropan-1-one; 2, 2-di-sec-butoxyacetophenone; 2, 2-dimethoxy-1, 2-diphenylethan-1-one; dimethoxy ketal; and phenylglyoxal 2,2' -diethoxyacetophenone, hydroxycyclohexylphenylketone, α -hydroxyketone, α -aminoketone, α -naphthylcarbonyl compound and β -naphthylcarbonyl compound, benzoin ethers (such as benzoin methyl ether), benzil ketals (such as benzil dimethyl ketal), acetophenone, fluorenone, 2-hydroxy-2-methyl-l-phenylpropan-1-one. Such UV initiators are commercially available, for example Irgacure 184, Irgacure 369, Irgacure LEX 201, Irgacure 819, Irgacure 2959Darocur 4265 or Degacure 1173 from Ciba, or visible light initiators: irgacure 784 and camphorquinone (Genocure CQ). In embodiments, the initiator may be a thermal initiator as described in patent publication WO 2011084141a 1.

In embodiments, the initiator may comprise one or more of 2,2' -azobis (2, 4-dimethylvaleronitrile), 2' -azobis (2-methylbutyronitrile), 4' -azobis (4-cyanovaleric acid), 2' -azobis [ N- (2-hydroxyethyl) -2-methylpropionamide ], 1' -azobis (cyclohexane-1-carbonitrile). Commercially available initiators, such as Vazo initiators, generally indicate the decomposition temperature of the initiator. In embodiments, initiators having decomposition points of about 50 ℃ or higher may be selected. In embodiments, the initiator is selected to stagger the decomposition temperatures of the various steps (pre-polymerization of the capsule shell material, shell formation, and hardening or polymerization). For example, the first initiator in the dispersed phase may decompose at 55 ℃ to facilitate prepolymer formation; the second initiator may decompose at 60 ℃ to aid in the formation of the shell material. Optionally, the third initiator may decompose at 65 ℃ to facilitate polymerization of the capsule shell material.

In embodiments, the total amount of initiator may be present in the dispersed phase in an amount of from about 0.001 wt% to about 5 wt%, or from about 0.01 wt% to about 4 wt%, or from about 0.1 wt% to about 2 wt%, based on the total weight of the dispersed phase. For example, the total amount of initiator may be present in the dispersed phase in an amount of about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 2, 3, 4, or 5 wt%.

In embodiments, and without intending to be bound by theory, it is believed that as the monomers begin to polymerize, the resulting polymer becomes insoluble in the dispersed phase and further migrates to the interface between the dispersed phase and the continuous phase.

In embodiments, the dispersed phase may include one or more benefit agents. In embodiments, the benefit agent may include perfumes, brighteners, insect repellents, silicones, waxes, flavors, vitamins, fabric softeners, skin protectants, UV blockers, enzymes, probiotics, dye polymer conjugates, dye clay conjugates, perfume delivery systems, sensates (cooling agents in one aspect), insect attractants (pheromones in one aspect), antimicrobials, dyes, pigments, bleaching agents, and mixtures thereof. In embodiments, the benefit agent may comprise a perfume or a perfume delivery system.

In embodiments, the dispersed phase may further comprise additional components, such as excipients, carriers, diluents, and other agents. In embodiments, the benefit agent may be mixed with an oil. In embodiments, the oil mixed with the benefit agent may include isopropyl myristate.

In embodiments, the dispersed phase may further comprise a processing aid. In embodiments, the processing aid may include one or more of a carrier, an aggregation inhibiting material, a deposition aid, and a particulate suspending polymer. Non-limiting examples of aggregation inhibiting substances include salts that can have a charge shielding effect around the particles, such as magnesium chloride, calcium chloride, magnesium bromide, magnesium sulfate, and mixtures thereof. Non-limiting examples of particle-suspending polymers include: polymers such as xanthan gum, carrageenan, guar gum, shellac, alginates, chitosan; cellulosic materials such as carboxymethyl cellulose, hydroxypropyl methyl cellulose, cationically charged cellulosic materials; polyacrylic acid; polyvinyl alcohol; hydrogenated castor oil; ethylene glycol distearate; and mixtures thereof.

According to an embodiment, the capsules may be produced according to the methods described herein.

Test method

When the encapsulated active is incorporated into a product, the sample formulation for analysis should produce an aqueous suspension of non-aggregated particles for analysis that does not alter the initial size distribution. For example, representative formulations may include those described in WO2018169531A1, pages 31-34, the disclosure of which is incorporated herein.

Capsule size and distribution testing method

The capsule size distribution was determined by Single Particle Optical Sensing (SPOS), also known as Optical Particle Counting (OPC), using an AccuSizer 780AD instrument and accompanying software CW788 version 1.82(Particle Sizing Systems, Santa Barbara, California, u.s.a.) or equivalent. The instrument is configured with the following conditions and options: flow rate 1 ml/sec; lower size threshold 0.50 μm; sensor model LE400-05 or equivalent; opening after automatic dilution; collecting time is 60 seconds; the number of channels is 512; the volume of the vessel fluid is 50 ml; maximum coincidence 9200. The measurement is started by flushing the sensor with water to a cold state until the background count is less than 100. Samples in suspension of the delivery capsules were introduced and the density of the capsules was adjusted with DI water by automatic dilution as required to obtain a capsule count of at least 9200/ml. The suspension was analyzed over a period of 60 seconds. The size range used is from 1 μm to 493.3. mu.m. Thus, the volume distribution and the number distribution are calculated as shown and described above.

From the cumulative volume distribution, a percentile 5 (d) is also calculated₅)、50(d₅₀) And 90 (d)₉₀) Is determined by the cumulative volume distribution, where the j percentage of the volume is cumulative

Delta rupture strength test method

To measure the Δ burst strength, three different measurements were made: i) volume weighted capsule size distribution; ii) the diameter of 10 individual capsules within each of the 3 specified size ranges, and; iii) the rupture force of the same 30 individual capsules.

a.) volume weighted capsule size distribution was determined by Single Particle Optical Sensing (SPOS), also known as Optical Particle Counting (OPC), using an AccuSizer 780AD instrument and accompanying software CW788 version 1.82(Particle Sizing Systems, Santa Barbara, California, u.s.a.) or equivalent. The instrument is configured with the following conditions and options: flow rate 1 ml/sec; lower size threshold 0.50 μm; sensor model LE400-05 or equivalent; opening after automatic dilution; collecting time is 60 seconds; the number of channels is 512; the volume of the vessel fluid is 50 ml; maximum coincidence 9200. The measurement is started by flushing the sensor with water to a cold state until the background count is less than 100. Samples in suspension of the delivery capsules were introduced and the density of the capsules was adjusted with DI water by automatic dilution as required to obtain a capsule count of at least 9200/ml. The suspension was analyzed over a period of 60 seconds. The resulting volume weighted PSD data is plotted and recorded and the values of the median, 5 th percentile and 90 th percentile are determined.

b.) the diameter and rupture force values (also known as burst force values) of each capsule were measured by a custom computer-controlled micromanipulator system with lenses and cameras capable of imaging the delivery capsules, and with a fine, flat-ended probe connected to a force sensor (such as model 403A available from Aurora Scientific Inc, Canada) or equivalent, as in Zhang, Z et al (1999) "Mechanical string of single microcapsules specified by a novel micromanipulation technique" j.microencapsulation, volume 16, phase 1, page 117 and in Sun, g, and Zhang, Z. (2001 Mechanical Properties of capsules-formed microcapsules ", j.microencapsulation, volume 18, page 5, page 3, and also in balance, balance of balance, 593, and available in balance k, balance of balance).

c.) a drop of the delivery capsule suspension was placed on a glass microscope slide and dried under ambient conditions for several minutes to remove water and obtain a sparse monolayer of individual capsules on the dried slide. The concentration of capsules in the suspension is adjusted as needed to obtain the appropriate capsule density on the slide. More than one slide preparation may be required.

d.) the slide is then placed on the sample holding stage of the micromanipulation instrument. Thirty benefit delivery capsules on the slide are selected for measurement such that ten capsules are selected within each of three pre-sized bands. Each size band refers to the capsule diameter derived from the volume weighted PSD generated by the Accusizer. The three size bands of capsules are: median diameter +/-2 μm; the 5 th percentile diameter +/-2 μm; and 90 th percentile diameter +/-2 μm. The capsules that developed deflation, leakage or damage were excluded from the selection process and no measurements were taken.

e.) for each of the 30 selected capsules, the diameter of the capsule was measured from the image on the micromanipulator and recorded. The same capsule was then compressed between two flat surfaces (i.e., a flat end force probe and a glass microscope slide) at a rate of 2 μm per second until the capsule broke. During the compression step, probe forces are continuously measured and recorded by the data acquisition system of the micromanipulation instrument.

f.) calculating the cross-sectional area (π r) of each of the selected capsules using the measured diameter and assuming spherical capsules²Where r is the radius of the capsule prior to compression). Determining the rupture force of each selected capsule from the recorded force probe measurements, as in: zhang, Z et al (1999) "Mechanical string of single microorganisms determined by a novel microorganism modulation technique" J.Microencapsulation, Vol.16, No. 1, page 117-.

g.) the rupture strength of each of the 30 capsules was calculated by dividing the rupture force (in newtons) by the calculated cross-sectional area of the respective capsule.

Using the recorded data, the delta burst strength was calculated

Where FS at di is the FS of the capsule at percentile i of the volume size distribution.

Shell thickness measurement test method

The capsule shell thickness in nanometers was measured for 20 benefit agent containing delivery capsules using a cryofracture cryo-scanning electron microscope (FFcryoSEM) at a magnification between 50000 and 150000 times. Samples were prepared by flash-chilling small volume suspensions of frozen capsules or finished products. Flash freezing can be achieved by immersion in liquid ethane, or by using devices such as 706802EM Pact type high pressure freezers (Leica Microsystems and Wetzlar, Germany) or equivalents. The frozen samples were fractured at-120 ℃ and then cooled to below-160 ℃ and lightly sputter coated with gold/palladium. These steps may be accomplished using low temperature manufacturing equipment such as those from gatan inc. (Pleasanton, CA, USA) or equivalents. The frozen, fractured and coated samples are then transferred to a suitable cryoSEM microscope such as Hitachi S-5200 SEM/STEM (Hitachi High Technologies, Tokyo, Japan) or equivalent at-170 ℃ or lower. In Hitachi S-5200, imaging was performed with 3.0KV accelerating voltage and 5 μ A to 20 μ A tip emission current.

Images of the fractured shells were taken in the form of cross-sectional views of 20 beneficial delivery capsules selected in a random manner that was not biased by their size to form representative samples exhibiting a distribution of capsule sizes. The shell thickness of each of the 20 capsules was measured using calibrated microscope software by drawing a measurement line perpendicular to the tangent to the outer surface of the capsule wall. 20 individual shell thickness measurements were recorded and used to calculate the average thickness, and the percentage of capsules having the selected shell thickness.

The diameter of the 20 cross-section capsules was also measured using calibrated microscope software by drawing a measurement line perpendicular to the capsule cross-section.

Effective volume core-shell ratio assessment

The effective volume core-shell ratio value is determined as follows, depending on the average shell thickness as measured by the shell thickness test method. The effective volume core-shell ratio of the capsules whose average shell thickness was measured was calculated by the following formula:

where the thickness is the shell thickness of an individual capsule and Dcaps is the diameter of the cross-sectional capsule.

Twenty independent effective volume core-shell ratios calculations were recorded and used to calculate the average effective volume core-shell ratio.

This ratio can be converted to a core-shell ratio score value by calculating the core weight percent using the following equation:

and the shell percentage may be calculated based on the following formula:

shell% — 100-core%.

Logarithmic (logP) test method for octanol/water partition coefficient

The log value (logP) of the octanol/water partition coefficient of each Perfume Raw Material (PRM) in the tested perfume mixtures was calculated. The logP (logPi) of the individual PRM was calculated using the Consensus logP calculation Model (Consensus logP Computational Model) version 14.02(Linux) or equivalent, available from Advanced Chemistry Development Inc. (Toronto, Canada), to provide dimensionless logP values. The Consensus log P Computational Model of ACD/Labs is part of the ACD/Labs Model suite.

The individual logP of each PRM was recorded to calculate the average logP of the perfume composition by using the following formula:

wherein xi is the weight% of the PRM in the perfume composition.

While particular embodiments of the present invention have been illustrated and described, it would be obvious to those skilled in the art that various other changes and modifications can be made without departing from the spirit and scope of the invention. It is therefore intended to cover in the appended claims all such changes and modifications that are within the scope of this invention. In the following examples, the apparatus used is shown in fig. 1 and 2.

Examples

An oil solution consisting of aromatic oil (44.86 wt%), isopropyl myristate (54.95 wt%), Vazo52(0.11 wt%) and Vazo67(0.07 wt%) was mixed at room temperature until the mixture was homogeneous.

A second oil solution consisting of aromatic oil (96 wt%) and Sartomer CN975 (hexafunctional aromatic urethane-acrylate oligomer, 4.00 wt%) was mixed at room temperature until the mixture was homogeneous.

An aqueous solution (continuous phase) was prepared by adding seviol 540(2 wt%) to RO water and heating to 90 ℃ for 4h with stirring and then cooling to room temperature.

Emulsions were prepared using the oscillating membranes and reactor apparatus of the invention. The start-up procedure was used with the continuous phase filling the chamber described in the figure (#) and flowing at a rate of 0.9 kg/min. The oscillatory displacement was 8mm and the frequency was 36 Hz. The two oil phases were mixed in-line using a static mixer at a ratio of 53.5:46.5 and passed through a triple filter cascade unit. The flow rate of the oil solution 1 was 0.321 kg/min. The flow rate of the oil solution 2 was 0.279 kg/min. The combined oil phase (dispersed phase) then entered the reactor and entered a manifold that evenly distributed the oil phase to each membrane sheet to pass through the membrane pores at a flux of 40kL/m2 h. Transmembrane pressure was measured at 2.6 psi.

As the dispersed phase passes through the oscillating membrane, droplets form and are sheared off the membrane surface to be stabilized by the continuous phase and carried away from the emulsion outlet. This is a continuous process. For a DP concentration of 40%, the continuous phase flow rate was 0.9 kg/min.

The obtained emulsion had an average droplet size of 26.5um and a coefficient of variation of the diameter based on volume distribution of 30.5%.

One kilogram of the emulsion was collected in a jacketed vessel and mixed using a paddle and overhead mechanical stirrer at 50 rpm. The temperature was raised to 60 ℃ at 2.5 ℃/min and held for 45 min. The temperature was then raised to 75 ℃ at 0.5 ℃/min and held for 240 minutes. The temperature was then raised to 90 ℃ at 0.5 ℃/min and held for 480 minutes. Finally, the batch was cooled to room temperature while maintaining stirring.

The final product is a suspension of encapsulated perfume capsules in a PVOH solution. Additional components such as stabilizers and/or preservatives may be added as desired.

The average volume size of the obtained capsule population was 29.7um, and the coefficient of variation of the diameter was 31.3%. The active fragrance content of the slurry was 32.97%.

The dimensions and values disclosed herein are not to be understood as being strictly limited to the exact numerical values recited. Rather, unless otherwise specified, each such dimension is intended to mean both the recited value and a functionally equivalent range surrounding that value. For example, a dimension disclosed as "40 mm" is intended to mean "about 40 mm".

Each document cited herein, including any cross referenced or related patent or patent application and any patent application or patent to which this application claims priority or its benefits, is hereby incorporated by reference in its entirety unless expressly excluded or otherwise limited. The citation of any document is not an admission that it is prior art with any disclosure of the invention or the claims herein or that it alone, or in combination with any one or more of the references, teaches, suggests or discloses any such invention. Further, to the extent that any meaning or definition of a term in this document conflicts with any meaning or definition of the same term in a document incorporated by reference, the meaning or definition assigned to that term in this document shall govern.

While particular embodiments of the present invention have been illustrated and described, it would be obvious to those skilled in the art that various other changes and modifications can be made without departing from the spirit and scope of the invention. It is therefore intended to cover in the appended claims all such changes and modifications that are within the scope of this invention.