METHOD FOR THE PREPARATION OF PARTICLES WITH CONTROLLED SHAPE AND/OR SIZE

Abstract

A method for preparation of liquid, semi-liquid or solid particles through formation of an initial emulsion and consecutive deformation and/or breakage of the particles by means of temperature change. The formed particles may further be polymerized, physically or chemically modified and/or functionalized. The shape and size of the particles depend on the oil used, the size of the emulsion droplets in the initial emulsion, the surfactant used and the cooling/heating rate or temperature, and finally the nature of the additives. The method allows the preparation of a diverse range of particle shapes: rod-like, with different aspect ratios (1a, 1b); triangular (1c); triangular with inscribed geometrical shapes (d); deformed and/or elongated triangular shapes (e, f); quadrilateral shapes (g, h); quadrilateral shapes with inscribed geometrical shapes (i); hexagonal (j); hexagonal with inscribed geometrical shapes (k, l); and/or polygonal shape (m).

Claims

1. A method comprising the steps of: a. preparing an emulsion of a hydrophobic phase in a hydrophilic phase to form droplets of the hydrophobic phase, where the hydrophobic phase is selected so that during cooling it transforms from a liquid state to a plastic state; and b. cooling the droplets to a temperature where the hydrophobic phase undergoes a phase transition from a liquid state to a plastic state.

2. The method according to claim 1, wherein the hydrophobic phase contains one or more of the following substances or classes of substances: linear hydrocarbon, cyclic hydrocarbon, asymmetric alkane, alkene, alkine, alcohol with one or more hydroxyl groups, ester, ether, amine, amide, aldehyde, ketone, fluoro-alkane.

3. The method according to claim 2, wherein the linear hydrocarbon molecules contain between 10 and 50 carbon atoms.

4. The method according to claim 3, wherein the hydrophobic phase is between 0.1 and 70 wt. %, with respect to the emulsion, wherein the hydrophobic phase comprises a mixture of hydrophobic substances.

5. (canceled)

6. The method according to claim 4, wherein the emulsion further comprises at least one oil dispersible component, wherein the concentration of oil dispersible component is up to 50 wt % with respect to a weight of the emulsion.

7. (canceled)

8. The method according to claim 1, wherein the emulsion contains at least one surfactant.

9. The method according to claim 8, wherein the surfactant is non-ionic.

10. The method according to claim 9, wherein the surfactant is an ethoxylated surfactant.

11. The method according to claim 8, wherein, the surfactant is an ionic surfactant.

12. The method according to claim 11, wherein the surfactant comprises one or a combination of alkyl bromide, alkyl sulfate, alkyl sulfonate, or betaine.

13. (canceled)

14. The method according to claim 12, wherein the concentration of surfactants is lower than 5 wt. % with respect to the weight of the emulsion.

15. The method according to claim 1, wherein the emulsion has an initial size of the droplets between 5 nm and 2 mm.

16. The method according to claim 1, wherein the method includes preparation of an initial emulsion through membrane emulsification, mechanical stirring, mechanical shaking or using homogenization equipment.

17. The method according to claim 8, wherein the surfactant comprises a hydrocarbon chain with a length equal or longer than a hydrocarbon chain of the hydrophobic phase.

18. The method according to claim 1, wherein the cooling step b) comprises cooling the droplets at a controlled cooling rate or cooling the droplets at a substantially fixed temperature.

19. The method according to claim 18, wherein the rate of cooling is between 0.0001 and 5 K per minute.

20. The method according to claim 1, further comprising a stage of solidifying the droplets, wherein the droplets are solidified by freezing or polymerization.

21. (canceled)

22. The method according to claim 1, wherein the temperature of the emulsion in emulsion forming step a) is higher than the melting temperature of the droplets.

23. The method according to claim 1, wherein the method further comprises one or more of functionalization of the droplets or encapsulation of the droplets.

24. The method according to claim 1, wherein there is a step of emulsion cooling and/or heating performed above the freezing point of the hydrophilic phase, wherein the hydrophilic phase comprises an anti-freezing component, wherein the anti-freezing component is up to 95 vol. % with respect to the emulsion volume.

25. (canceled)

26. (canceled)

27. The method according to claim 24, wherein the step of emulsion cooling occurs by achieving a temperature below the freezing temperature of the droplets.

28. The method according to claim 27, wherein the method further comprises subjecting the emulsion to a temperature change to cause a decrease of droplet size by droplet breakup during one or more cycles of emulsion cooling and/or heating.

29. (canceled)

30. The method according to claim 28, wherein the method yields submicron droplets or particles.

31. The method according to claim 28, wherein upon heating drop breakup occurs by dewetting of parts of the melted hydrophobic phase from the its frozen crystal form.

32. The method according to claim 1, wherein the droplets are isolated from the hydrophilic phase.

33. The method according to claim 1, wherein the droplets are modified by one or more of: polymerization, encapsulation, surface or bulk-modification; and/or functionalization, wherein the droplets are modified before or after the cooling step b).

34. (canceled)

35. A dispersion of liquid, semi-liquid or solid particles obtained or obtainable from the method of claim 1.

36. A solid particle obtained or obtainable from the method of claim 1.

Description

DRAWINGS DESCRIPTION

[0107] FIG. 1 The method allows the preparation of a diverse range of particle shapes: rod-like, with different aspect ratios (1a, 1b); triangular (1c); triangular with inscribed geometrical shapes (d); deformed and/or elongated triangular shapes (e, f); quadrilateral shapes (g, h); quadrilateral shapes with inscribed geometrical shapes (i); hexagonal (j); hexagonal with inscribed geometrical shapes (k, l); and/or polygonal shape (m).

[0108] FIG. 2 illustrates the experimental set up, used in Example 1. The emulsion [301] is put in a capillary [302]. The capillary is put in a thermostating chamber [303], which is being cooled or heated via circulating liquid [304, 305], while monitored in a microscope [306].

[0109] FIG. 3 illustrates some of the geometrical shapes of the solid particles, prepared via the current method.

[0110] FIG. 4 shows the size of the drops in the initial emulsions and after two cycles of freezing and melting of the droplets. Scale, 20 m, d.sub.32 is the Sauter diameter of the drops.

[0111] FIG. 5 shows pictures of particles, prepared via the current method. The particles are made from hexadecane in the presence of 1.5 wt % surfactant: (a-d) Tween 60, (e) Brij 58 (f-h) Tween 40. (a-d) Consequent phases of deformation of droplets, stabilized with Tween 60. (e) Rod-like particles, after freezing. (f) Frozen triangles with elongated edges. (g) Frozen parallelograms. (g) Toroidal particles. The initial size of the droplets is indicated on the picture and the cooling rates are between 0.5 and 2.0 degrees Celsius.

TERMINOLOGY

[0112] Emulsion is a mixture of two immiscible liquids, whereas one is dispersed in the other in the form of droplets. Generally, the emulsion is made of polar (hydrophilic) phase, e.g. water, and non-polar (hydrophobic) phase, which is called oil. In accordance to the Bancroft rule, when the surfactant, used for the stabilization of the droplets, is more soluble in the water phase, then the expected emulsion type is oil-in-water. Water soluble surfactants have hydrophilic-lipophilic balance (HLB) >10, for example 30>HLB>14 (e.g. 18>HLB>14).

[0113] Immiscible means that after mixing there is more than one component and more than one phase. One of the components could be partially soluble into the other components but at least two separate phases should be present.

[0114] The words drop, droplet and particle to be considered interchangeable for the purposes of the current invention.

[0115] The word surfactant should be understood as single or multiple surfactants. Surfactants are class of molecules with amphiphilic naturepolar group (head) and non-polar group (tail). The head could be ionic or non-ionic. The tail is usually a hydrocarbon sequence. They could be oil or water soluble. Surfactants with HLB<10 are oil soluble and those with HLB >10 are water soluble.

[0116] Initial emulsion is used for the preparation of drops with specific shape and/or breakage into smaller droplets. The initial emulsion consists of oil drops, dispersed in water in presence of surfactant and could be prepared via any other method, including membrane emulsification, high pressure homogenization, rotor-stator homogenization, stirred vessels, magnetic or non-magnetic stirring devices, etc.

[0117] Membrane emulsification is a method for injecting one phase into the other by the means of applied pressure (see Examples).

[0118] In this invention the expressions rotator phase; plastic crystal; polymorphic transition; and liquid-crystal to be considered synonyms. They are characterized with translational symmetry of the molecules, which however have rotational freedom. (see Sirota, E. B., Herhold, A. B. Transient phase-induced nucleation. Science 283, 529-532 (1999); Ueno, S., Hamada, Y., Sato, K. Controlling Polymorphic Crystallization of n-Alkane Crystals in Emulsion Droplets through Interfacial Heterogeneous Nucleation. Cryst. Growth Des. 3, 935-939 (2003)). Their presence could be detected via X-ray diffraction.

Examples of Surfactant:

Nonionic Surfactants:

[0119] Polyoxyethylene glycol alkyl eter: CH.sub.3(CH.sub.2).sub.7-16(OC.sub.2H.sub.4).sub.1-25OH, e.g. octa- or penta-ethyleneglycol monodecyl ether; Polyoxypropylene glycol alkyl ethers CH.sub.3(CH.sub.2).sub.10-17(OC.sub.3H.sub.6).sub.1-25OH; Glycoside alkyl ether CH.sub.3(CH.sub.2).sub.10-17(O-Glucoside).sub.1-3-OH, e.g. decyl- or lauryl-glucoside; Polyoxyethyle glycol octylphenol eters: C.sub.8H.sub.17(C.sub.6H.sub.4)(OC.sub.2H.sub.4).sub.1-25OH, e.g. Triton X-100; Polyoxyethylene glycol alkylphenol eters: C.sub.9H.sub.19(C.sub.6H.sub.4)(OC.sub.2H.sub.4).sub.1-25OH, for instance Nonoxynol-9; glycerol alkyl esters like glyceryl laurate; Polyoxyethylene glycol sorbitan alkyl esters. Polysorbates; Sorbitan alkyl esters, for example Span; Cocamide DEA, Cocamide MEA, dodecylmethylamine oxide, copolymers of polyoxyethylene glycol and propylene glycol, for instance Poloxamer; and polyoxyethylene amine.

Cationic Surfactants:

[0120] Including alkyl trimethyl ammonium salts, e.g. cetyltrimethyl ammonium bromide, cetyltrimethyl ammonium chloride, cetylpyridinum chloride, alkyl dimethyl benzyl ammonium chloride, 5-bromo-5-nitro-1,3-dioxane, dimethyl dioctyl ammonium chloride, cetrimide, dioctyl decyl methyl ammonium bromide, etc.

Anionic Surfactants:

[0121] Including ammonium lauryl sulfate, sodium dodecyl sulfate and similar alkyl eter sulfates with different chain length.

Amphoteric Surfactants:

[0122] Examples include cocamidopropyl betaine, lauryl betaine, sulfobetaine and their derivatives.

[0123] Oil soluble surfactants are some non-ionic surfactants with HLB <10, e.g. sorbitan esters of fatty acids (polysorbates), such as Span 40, Span 60, Brij 52, etc.

[0124] The shape of the particles, prepared through the method presented in this invention, depends on the chemical composition of the dispersed phase (droplets), the initial size of the droplets, the choice of surfactant, the cooling/heating rate or temperature. Additional information is included in the EXAMPLES section.

[0125] The controlled rate of cooling/heating is the temperature difference applied by us for a period of time, divided by the time. The rate could be changed, kept constant or could be zero.

[0126] Thermostated vesselin the current invention thin glass capillaries were used, fitted in a metal plate. There is circulating fluid (FIG. 2), which has a temperature, controlled via cryo-thermostate. The method is not limited to capillaries. Vessels could be beakers, cylinders, centrifugal tubes, pipes, etc., as long as their temperature can be changed in a predefined manner.

[0127] Rotator phases could be formed from alkanes, alkenes, alkines, alcohols with one or more hydroxyl groups, esters (mono-, di-, tri-, etc.), eters, amides, amines, aldehydes, ketones, nitriles, fluorinated hydrocarbons, mixtures of them (e.g. carboxylic acids, or a mixture of alcohol and aldehyde or ketone), pyrrolidinium salts and derivatives, imidazolium salts and derivatives, etc. The rotator phases must be at least partially insoluble in the hydrophilic phase.

[0128] Solid organic particles with anisotropic shape are particles, prepared from any of the aforementioned substances or mixture of substances, which yield shape of the particles different from spherical (which may be the preferred form of small drops in liquids).

[0129] Aspect ratio is the relation between the longest projections of the particles, divided by the initial size of the drops, before their deformation. High-aspect ratio is aspect ratio of 5 or more, wherein it could be more than 100.

[0130] The current invention uses oil-in-water emulsions for initial emulsions. They are used to produce emulsions with much smaller size of the droplets, e.g. submicron size but not limited to; and/or for control of the particle shape.

[0131] The initial emulsion is prepared via any other method. The emulsion contains oil droplets, dispersed in water or in water-containing solution or in mixture of hydrophilic phases. The deformation of the droplets depends on the applied temperature, the oil chosen, the drop size, waiting time, etc.

[0132] The choices of surfactant and oil define if the drops are going to break into smaller ones, but are not the only limiting factors. The drop breakage could occur during the cooling or during the melting of already frozen or deformed particles. The temperature of breakage is system specific and it could be higher or lower than the melting/freezing temperature of the bulk phase.

[0133] The method requires different temperatures and temperature intervals, depending on the oil, surfactant, drops size, etc. For instance, the preparation of tetradecane droplets with different shapes requires working between 273 and 280 K, while for hexadecane it is necessary to work in between 282 and 291 K and for eicosane-between 303 and 308 K for droplets with the same size and surfactant.

[0134] One of the potential applications is the enhanced control over rheological properties of emulsions and suspensions. Using the method described here allowed preparation of particles with high aspect ratios, which could increase the viscoelastic response several orders of magnitude even at low concentrations of the dispersed phase.

[0135] Other applications include pharmacy and food sectors. Both sectors often use temperature-sensitive components, such as vitamins, which should not be heated. This method allows working at ambient or lower temperatures and narrow temperature intervals.

[0136] The method does not require the use of volatile solvents; it has a high yield and requires low energy consumption compared to conventional shear methods.

EXAMPLES

[0137] Alkanes, used in the current invention are purchased from Sigma-Aldrich and have analytical purity, 99%. Additional purification of alkanes was performed by the means of silicagel column (Florisil). The interfacial tension of the alkanes used in the current study was 50 mN/m, depending on the specific hydrocarbon used. In presence of surfactants the interfacial tension was between 2 and 10 mN/m at temperatures close to the freezing temperature of the drops.

[0138] Emulsions were prepared with membrane emulsification in presence of 1.5 wt % water soluble surfactant. The amount of surfactant was calculated with respect to the water phase. The oil droplets were generated by the means of glass membranes (Shiratzu porous glass). Membranes had different size of monodisperse poresgenerally: 1, 2, 3, 5 or 10 m. In the membrane there was oil phaseupon applying pressure, the oil started moving through the membrane in the water phase, thus forming monodisperse droplets of oil-in-water. The surfactants dissolved in the water phase were selected to have HLB >14, e.g. Brij 58 has HLB of 15.7; Brij 78-HLB=15.3; Tween 40 has HLB=15.5; and Tween 60 has HLB 14.9.

[0139] Emulsions were put in capillaries50 mm long, 1 mm wide and 0.10 mm high. The capillaries were put in a thermostated vessel, consisting of a metal plate with water circulating through it. The vessel is connected to a cryo-thermostate (Julabo CF30), allowing high precision temperature control (accuracy 0.2 C.).

[0140] During the cooling/heating of the emulsions a microscope Axioplan or Axiolmager.M2m (Zeiss, Germany) was used in transmitted white, polarized light. The microscopes were equipped with plate, set at 45 in between the analyzer and the polarizer. The observations were held by the means of long-distance objective with 20, 50 or 100 times magnification. The size of the drops and particles was determined from the microscopic images.

[0141] The surfactants are a class of substances, consisting of a polar part (head) and non-polar part (tail). The tail usually consists of a hydrocarbon segment, while the head consist of a functional group, which could be either ionic or non-ionic. As a result of its structure, the surfactant has amphiphilic naturehydrophobic tail and hydrophilic head. As a rule, surfactants with tails similar or longer than the used hydrocarbon (in the case of alkanes) have a higher freezing temperature than the alkane itself. As a result, during the cooling of the emulsions the surface hardens and changes the shape of the droplets.

[0142] The cooling rate affects the observed phenomenon significantly. At cooling rates lower than 5 degrees Celsius, the emulsion droplets change their shape significantly. For example, the emulsions prepared in the presence of 1.5 wt. % Brij 58 and hexadecane form polyhedra initially. The polyhedra gradually evolve in series of different shapes: hexagonal prisms, then quadrupolar prisms, elongated quadrupolar prisms with high aspect ratio and in the end they become fibers. Each of the stages of the drop shape evolution could be used for preparation of particles, either by freezing or via vitrification. The yield of the different shapes, however, differs: Brij 58 enables yields as high as 755% for quadrupolar prisms and 255% for triangular ones; or 905% for high-aspect ratio quadrupolar prisms; or 905% for fibrilar structures, depending on the different ways of preparation. Tween 60 allows preparation of more than 90% rod-like particles.

[0143] The shape of the particles depends on the size of the droplets in the emulsions. At higher rates of cooling, e.g. 5 K/min, depending on the surfactant used, the largest drops often freeze without shape transformations.

Example 1Preparation of Particles with Different Aspect Ratios

[0144] The current example demonstrates the preparation of solid particles with different aspect rations, as illustrated in FIG. 1. The nonionic surfactant, Tween 40, is dissolved into water. Its concentration is 1.5 wt. % with respect to the mass of water. Then hexadecane droplets with diameter 15 m are injected into the water phase. The concentration of the droplets is 1 vol. % with respect to the whole amount of emulsion. The emulsion [301] is put in a capillary [302] and put in thermostated chamber [303]. There is cooling liquid which circulates throughout the vessel [304, 305].

[0145] The initial temperature is 298 K and the cooling rate is 1.4 K/min. As a result the drops deform to hexagonal prisms and then freeze. Their aspect ratio (final-to-initial length ratio) is 4. The initial temperature is 298 K and the cooling rate is 0.16 K/min. As a result the drops deform to rod-like or fibrilar particles. Their aspect ratio (final-to-initial length ratio) is higher than 50. The yield is around 90% in number of particles for both cooling rates.

Example 2Preparation of Submicron Drops and/or Particles

[0146] This example demonstrates the drop-size reduction, which is illustrated in FIG. 4. 0.6 wt. % Brij 58 is dissolved in water and 0.4 wt. % Brij 52 is dissolved in hexadecane. The hexadecane is dispersed in water in volume ratio 1:3, through membrane emulsification. The emulsions are cooled down from 298 to 278 K in a fridge and then heated back up to 298 K. After two cycles the final drop size 0.9 m in diameter. Depending on the final temperature, the droplets could be liquid or solid.

Example 3Polymerization

[0147] The current example demonstrates the preparation of polymerized particles with different geometrical shapes, as demonstrated in FIG. 1. The nonionic surfactant, Tween 40, is dissolved into water. Its concentration is 0.15 wt. % with respect to the mass of water. Then stearyl methacrylate droplets with diameter 10 m are injected into the water phase. The concentration of the droplets is 1 vol. % with respect to the whole amount of emulsion. The emulsion [301] is mixed with water soluble component-ketoglutaric acid, e.g. 1.75 wt. % with respect to the water phase; then put in a capillary, and finallyput in thermostated chamber.

[0148] The initial temperature of the emulsion is 298 K and the temperature in the cooling chamber is 2923 K. As a result from the initial spherical drops undergo a transition into hexagonal prisms within 0 to 15 minutes or triangular prisms, when t >10 min. The liquid prisms could be polymerized via irradiation with UV light at 365 nm, or left to change shape and then polymerized. Yield was more than 80% hexagonal prisms (by number of drops converted in prisms) or more than 50% triangular prisms.

Example 4Composite Formation

[0149] Ferrofluid or hydrophobic ceramic nano-particles with concentration 2 wt % are dispersed in stearyl methacrylate. Then procedure in example 3 is followed.

Example 5Tuning Surface Chemistry and Morphology (Growing Spikes or Brushes)

[0150] The nonionic surfactant, Tween 40, is dissolved into water. Its concentration is 10-16 wt. % with respect to the mass of water. Then stearyl methacrylate droplets with diameter 35 m are injected into the water phase. The concentration of the droplets is 1 vol. % with respect to the whole amount of emulsion. The emulsion [301] is mixed with water soluble component-ketoglutaric acid, e.g. 0.5 wt. % with respect to the water phase; then put in a capillary [302], and finallyput in thermostated chamber [303].

[0151] The initial temperature of the emulsion is 298 K and the temperature in the cooling chamber is 3083 K. The liquid drops are polymerized via irradiation with UV light at 365 nm for 30-60 min with UV LED. Then, emulsion/suspension is cooled down to 2923 K and left for few hours. Spike with different size and density are grown based on time for cooling. For example, 10 wt % Tween 40 gives at least 5 m spikes (brushes) within 5 hours of waiting.

Example 6Organic Encapsulation of Oil-Soluble Components

[0152] The nonionic surfactant, Tween 40, is dissolved into water. Its concentration is 0.3 wt. % with respect to the mass of water. Then stearyl methacrylate droplets with diameter 10 m are injected into the water phase. The methacrylate droplets might contain any of the listed oil soluble components, but not limited to them:

[0153] Trimethylolpropane methacrylate up to 10 wt %, for example 5 wt %

[0154] Methacrylic acid up to 25 wt %, and for example 5 wt %

[0155] Acrylic acid up to 25 wt %, and for example 5 wt %

[0156] The emulsion is mixed with water soluble component-ketoglutaric acid, e.g. 1.75 wt. % with respect to the water phase; then put in a capillary, and finallyput in thermostated chamber.

[0157] The initial temperature of the emulsion is 298 K and the final temperature depends on the amount of added components and the component type: typically between 273 and 353 K. The liquid drops are polymerized via irradiation with UV light at 365 nm for 15-30 min with UV.