WO2009068673A1 - Inkjet printer for the manufacture of emulsions - Google Patents

Inkjet printer for the manufacture of emulsions Download PDF

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Publication number
WO2009068673A1
WO2009068673A1 PCT/EP2008/066476 EP2008066476W WO2009068673A1 WO 2009068673 A1 WO2009068673 A1 WO 2009068673A1 EP 2008066476 W EP2008066476 W EP 2008066476W WO 2009068673 A1 WO2009068673 A1 WO 2009068673A1
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WO
WIPO (PCT)
Prior art keywords
emulsion
immiscible substance
substance
immiscible
inkjet
Prior art date
Application number
PCT/EP2008/066476
Other languages
German (de)
French (fr)
Inventor
Stephan FÖRSTER
Stephan Hauschild
Original Assignee
Centrum Für Angewandte Nanotechnologie Gmbh
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Centrum Für Angewandte Nanotechnologie Gmbh filed Critical Centrum Für Angewandte Nanotechnologie Gmbh
Publication of WO2009068673A1 publication Critical patent/WO2009068673A1/en

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Classifications

    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01FMIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F23/00Mixing according to the phases to be mixed, e.g. dispersing or emulsifying
    • B01F23/40Mixing liquids with liquids; Emulsifying
    • B01F23/41Emulsifying
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01FMIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F23/00Mixing according to the phases to be mixed, e.g. dispersing or emulsifying
    • B01F23/40Mixing liquids with liquids; Emulsifying
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01FMIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F23/00Mixing according to the phases to be mixed, e.g. dispersing or emulsifying
    • B01F23/40Mixing liquids with liquids; Emulsifying
    • B01F23/405Methods of mixing liquids with liquids
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01FMIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F23/00Mixing according to the phases to be mixed, e.g. dispersing or emulsifying
    • B01F23/40Mixing liquids with liquids; Emulsifying
    • B01F23/45Mixing liquids with liquids; Emulsifying using flow mixing
    • B01F23/451Mixing liquids with liquids; Emulsifying using flow mixing by injecting one liquid into another
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01FMIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F25/00Flow mixers; Mixers for falling materials, e.g. solid particles
    • B01F25/50Circulation mixers, e.g. wherein at least part of the mixture is discharged from and reintroduced into a receptacle
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01FMIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F33/00Other mixers; Mixing plants; Combinations of mixers
    • B01F33/45Magnetic mixers; Mixers with magnetically driven stirrers
    • B01F33/452Magnetic mixers; Mixers with magnetically driven stirrers using independent floating stirring elements
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01FMIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F35/00Accessories for mixers; Auxiliary operations or auxiliary devices; Parts or details of general application
    • B01F35/71Feed mechanisms
    • B01F35/712Feed mechanisms for feeding fluids
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01FMIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F35/00Accessories for mixers; Auxiliary operations or auxiliary devices; Parts or details of general application
    • B01F35/71Feed mechanisms
    • B01F35/717Feed mechanisms characterised by the means for feeding the components to the mixer
    • B01F35/7179Feed mechanisms characterised by the means for feeding the components to the mixer using sprayers, nozzles or jets
    • B01F35/71791Feed mechanisms characterised by the means for feeding the components to the mixer using sprayers, nozzles or jets using ink jet heads or cartridges, e.g. of the thermal bubble jet or piezoelectric type

Definitions

  • the present invention discloses a method for the manufacture of an emulsion using an inkjet device.
  • US Patent No. US 6123861 is titled "Fabrication of microchip drug delivery devices" (inventors John T Santini, Michael J Cima and S. Langer)
  • the US Patent No. US 6123861 is assigned to Massachusetts Institute of Technology, Cambridge Mass. USA.
  • the US 6123861 document teaches fabrication methods of microchips that control both the rate and time of release of multiple chemical substances used in the pharmaceutical indus- try and allow for the release of a wide variety of molecules in either a continuous or pulsatile manner.
  • a release system which includes the molecules to be delivered, is inserted into reservoirs by injection, inkjet printing, or spin coating methods.
  • the US 6123861 document exemplifies the use of medicinal compounds and their use within inkjet technology.
  • the US 6123861 patent is directed to the efficacy of drug administration.
  • US Patent publication No. 2004/0181196 is titled "Cutaneous administration system”.
  • the US 2004/0181196 document (inventors Ray L Pickup, Clement C Lo and William D Noonan) is assigned to The Hewlett-Packard Company, USA.
  • This US 2004/0181196 document describes the cutaneous administration of bio-active agents by a jet dispenser using inkjet technology.
  • the jet dispenser propels precise volumes of the bio- active agent towards the skin, where the bio-active agents exert their effect.
  • International Patent application No. WO2006/044695 is titled "InkJet dispenser for automated drug administration in a hospital management system” (inventors Vitello C. John, Welkley Steve, Evans Andrew and Greeven John).
  • the WO 2006/044695 document also describes the cutaneous administration of bio-active agents by a jet dispenser using inkjet technology.
  • the inkjet dispenser propels precise volumes of a bio-active agent towards the skin, where the bio-active agents exert their effect.
  • the Fletcher article discloses a method for the manufacture of microspheres that are mono-disperse polymer particles by using a "sphere-jet” system.
  • the "sphere-jet” system is a drop on demand inkjet printer with a piezoelectric driven tip consisting of a micro capillary with a 50 ⁇ m orifice diameter.
  • the inkjet printer of Fletcher is submerged under water and is used to extrude a polymer- analyte solution.
  • the particle size is controlled by the concentration of the polymer, fluid feed rate and the applied frequency.
  • the mono-disperse polymer particles are manufactured by an oil- water emulsion reaction.
  • An emulsion is a mixture of two immiscible or unblendable substances. Emulsions are part of a more general class of two-phase systems of matter called colloids.
  • the term colloid and emulsion are sometimes used interchangeably, the term emulsion tends to im- ply that both a dispersed phase of the emulsion and a continuous phase of the emulsion are a liquid.
  • An emulsif ⁇ er (also known as an emulgent or surfactant) is a substance which stabi- uses an emulsion.
  • An example of food emulsifiers are egg yolk (where the main emulsifying chemical is the phospholipid lecithin) and mustard where a variety of chemicals in the mucilage surrounding the seed hull act as the emulsif ⁇ er; proteins and low-molecular weight emulsifiers are also common. Particles can also stabilise the emulsion through a mechanism called Pickering stabilization.
  • Detergents are another class of emulsifier that will chemically interact with both oil and water, stabilising the interface between the oil or water droplets in the emulsion. This principle is exploited in soap to remove grease for the purpose of cleaning.
  • emulsions examples include milk (fat dispersed in water), butter (water dis- persed in fat), mayonnaise (oil dispersed in water which is stabilised with the emulsifier lecithin) and ice-cream (fat in water which is then frozen).
  • milk fat dispersed in water
  • butter water dis- persed in fat
  • mayonnaise oil dispersed in water which is stabilised with the emulsifier lecithin
  • ice-cream fat in water which is then frozen.
  • Emulsions are also used as drug delivery systems such as Propofol which is a liquid anaesthetic dissolved in oil.
  • Emulsions are conventionally manufactured by the shear- induced break-up of macroscopic liquid droplets of a disperse phase into a continuous phase.
  • the shear is provided by mechanical methods such as shaking, stirring, homogenising or ultrasound.
  • Emulsions are generally unstable and thus do not form spontaneously. Generally for the manufacture of most emulsions, high shear forces are needed with a corresponding intake of a large amount of energy to either the disperse phase or the continuous phase of the manufactured emulsion.
  • the energy intake by the emulsion usually results in a considerable amount of damage to the immiscible substances used to manufacture the emulsion or to damage to the manufactured emulsion itself.
  • damage can be mechanical damage and may lead to denaturisation of bio-molecules, cleavage damage of chemical compounds or the damage can be due to a result of an increase in temperature within the immiscible substances due to the energy intake in the emulsion manufacturing process.
  • InkJet cartridges provide a means to generate very small substance droplets.
  • the droplet volumes can be down to picolitres (10 ⁇ 12 litres).
  • a jet of droplets from an inkjet cartridge can be injected into a liquid to produce emulsions with dispersed droplets which have diameters in a typical range of 10 - 500 nm.
  • a method for the manufacture of the emulsion using the inkjet cartridge avoids the use of the harsh mechanical methods outlined above.
  • the method for the manufacture of emulsions using the inkjet cartridge provides a means to manufacture the emulsion that contains sensitive compounds in a gentle environment, such that the sensitive compounds are not damaged by conventional emulsion manufacturing methods.
  • the present invention teaches a method and an apparatus for the manufacture of an emulsion, preferably but not limited to the emulsion containing a bio-active substance.
  • the method comprises providing a first immiscible substance of the bio-active substance in at least one inkjet cartridge and providing a second immiscible substance in a container.
  • An emulsif ⁇ er may be present in the inkjet cartridge and/or in the container.
  • the first immiscible substance is printed through an inkjet printhead which is located above the surface of the second immiscible substance.
  • the first immiscible substance emerges as a droplet jet from the inkjet printhead into the container where the second immiscible sub- stance is present.
  • the first immiscible substance forms the emulsion with the second immiscible substance in the container.
  • the method allows for the manufacture of the emulsion at various temperatures.
  • the ability to control the temperature of either the first immiscible substance and/or the second immiscible substance is used to alter the viscosity of either first immiscible substance and/or the second immiscible substance during the manufacture of the emulsion.
  • the method allows for the manufacture of a wide range of emulsions that would usually prove problematic.
  • the invention allows for the use of co-solvents.
  • the co-solvents are used to reduce the viscosity of the immiscible substances and also allows the preparation of emulsions at various temperatures to aid the manufacture of the emulsions.
  • co-solvents can be used, they are removed from the manufactured emulsion by a dialysis or other techniques such as rectification, adsorption or stripping.
  • the invention provides for the manufacture of emulsions without affecting the chemical properties of either the first immiscible substance or the second immiscible sub- stance.
  • the method and the apparatus allow for the manufacture of bio-active emulsions efficiently, quickly and in large quantities without affecting their chemical properties.
  • the invention provides for the continuous manufacture of the emulsion allowing large quantities of the emulsion to be manufactured, which may not be have been previously possible by using co-solvents, warming means and dialysis for the manufacture of the emulsion.
  • Figure 1 Depicts the manufacture of emulsions using inkjet devices in a batch preparation system.
  • Figure 2. Depicts the manufacture of emulsions using inkjet devices in a continu- ous flow system.
  • Figure 3. Depicts a schematic flow diagram for the manufacture of emulsions using inkjet devices.
  • Figure 4 Shows a size distribution by intensity of soy bean oil (A) emulsion.
  • Figure 5 Shows a size distribution by intensity of soy bean oil (A) emulsion after 3 weeks.
  • Figure 6 Shows a size distribution by intensity of soy bean oil emulsions with various concentrations (15% - A, 3% - B, 1% - C, all concentrations in % by weight) of soy bean oil in the cartridge/printhead.
  • Figure 7 Shows a size distribution by intensity of soy bean oil (15%) emulsion stabilised by sodium dodecyl sulphate (SDS) after preparation (A) and after 5 weeks (B).
  • SDS sodium dodecyl sulphate
  • Figure 8 Shows a size distribution by intensity of soy bean oil (5%) emulsion stabilised by sodium dodecyl sulphate (SDS) after preparation (A) and after 5 weeks (B).
  • SDS sodium dodecyl sulphate
  • Figure 9 Shows a size distribution by intensity of soy bean oil (15%) emulsion stabilised with various surfactants, sodium dodecyl sulphate (SDS) (A), egg lecithine (B) and cetyltrimethylammonium bromide (CTAB) (C) (each 3%) - after preparation.
  • SDS sodium dodecyl sulphate
  • B egg lecithine
  • C cetyltrimethylammonium bromide
  • Figure 10 Shows a size distribution by intensity of soy bean oil (15%) emulsion stabilised by sodium dodecyl sulphate (SDS) (A), sodium laureth sulphate (SLES) (B) and sodium dodecyl benzene sulphonate (SDBS) (C) (each 3%) after preparation.
  • SDS sodium dodecyl sulphate
  • SLES sodium laureth sulphate
  • SDBS sodium dodecyl benzene sulphonate
  • Figure 11 Shows a size distribution by intensity of soy bean oil (15%) emulsion stabilised with various surfactants, sodium dodecyl sulphate (SDS) (A), sodium laureth sulphate (SLES) (B) and sodium dodecyl benzene sulphonate (SDBS) (C) (each 3%) - after 3-5 weeks.
  • Figure 12. Shows a size distribution by intensity of soy bean oil (15%) emulsion at various temperatures, stabilised by lecithin (3%) at 6 0 C (A), 15 0 C (B) and 35 0 C (C) - after preparation.
  • Figure 13 Shows a size distribution by intensity of soy bean oil (15%) emulsion at various temperatures stabilised by lecithin (3%) at 6 0 C (A), 15 0 C (B) and 35 0 C (C) - 3-5 weeks after preparation.
  • Figure 14 Shows a size distribution by intensity of various oil emulsions, of lin- seed oil (A), sweet almond oil (B) and fish oil (C) (each 15%) - stabilised by lecithin (3%) after preparation.
  • Figure 15 Shows a size distribution by intensity of various oils - (15%) stabilised by lecithin (each 3%) and equipped with coriander oil (A), orange oil (B) and menthol (C) ( 1 %) after preparation.
  • Figure 16 Shows a size distribution by intensity of fragrant emulsions of soy bean oil (15%) stabilised by lecithin (3%) and equipped with coriander oil (A), carnation oil (B) and cayenne pepper extract (C) (each 1%) after preparation.
  • coriander oil A
  • carnation oil B
  • cayenne pepper extract C
  • Figure 17 Shows a size distribution by intensity of emulsions containing various active ingredients with soy bean oil (15%) stabilised by lecithin (3%) equipped with tocopherol (A), clotrimazol (B) and piroxicam (C) - (each 1%) after preparation.
  • Figure 18 Shows size distribution by intensity of emulsions with concentrations of 15% (A), 5% (B) and 2% (C) of paraffin oil in the cartridge stabilised by sodium dode- cyl sulphate (SDS) (3%) after preparation
  • Figure 19 Shows a size distribution by intensity of paraffin oil (15%) emulsion stabilised by - sodium dodecyl sulphate (SDS) (A), sodium dodecyl benzene sulphate (SDBS) (B) and sodium laureth sulphate (SLES) (C) (3%) after preparation.
  • Figure 20 Shows a size distribution by intensity of paraffin oil (5%) emulsion stabilised by - sodium dodecyl sulphate (SDS) with concentrations of 3% (A) and 5% (B) after preparation.
  • Figure 21 Shows a size distribution by intensity of oil (15%) emulsion stabilised by lecithin (3%) printed from 2-propanol (A), ethanol (B) and tetrahydrofuran (THF) (C).
  • Figure 22 Shows a size distribution by intensity of soy bean oil (15%) emulsion stabilised by lecithin (3%) printed from one printer (A) and two printers (B).
  • Figure 23 Shows a size distribution by intensity of soy bean oil (15%) emulsion stabilised by lecithin (3%) printed from printer model #1 (A) and printer model #2 (B).
  • Figure 24 Shows a size distribution by intensity of soy bean oil (15%) emulsion stabilised by lecithin (3%) printed into various shapes of container, shape #1 (A), shape #2 (B) and shape #3(C).
  • Figure 25 Shows a size distribution by intensity of soy bean oil (15%) emulsion stabilised by lecithin (3%) printed in water under various pump speeds, speed #1 (A), speed #2 (B) and speed #3 (C) of the first closed loop.
  • Figure 26 Shows a size distribution by intensity of soy bean oil (15%) emulsion stabilised by lecithin (3%) printed in water under co-solvent removal continuously during preparation (A) and after preparation (B) via dialysis apparatus.
  • Figure 27 Shows a size distribution by intensity of soy bean oil (15%) emulsion stabilised by lecithin (3%) printed in water using thermal inkjet printers (#1, A and #2, B) and piezo inkjet (C) printers.
  • Figure 28 Shows a size distribution by intensity of soy bean oil (15%) emulsion stabilised by lecithin (3%) printed in water equipped with dye Sudan IV (A) and without dye (B).
  • Figure 29 Shows a size distribution by intensity of water in oil emulsion stabilised by polyethylene glycol octylphenol ether (Triton X-IOO) printed in paraffin oil (A).
  • the present invention teaches a method 300 and an apparatus 100, 200 for the manufacture of an emulsion 125 utilising an inkjet cartridge 110.
  • the inkjet cartridge 110 is preferably a thermal inkjet cartridge.
  • the inkjet printhead 120 is preferably a thermal inkjet printhead.
  • the invention is, however, not limited to a particular inkjet technology and incorporates all such known technologies such as thermal inkjet, piezoelectric inkjet, (solenoid) valve inkjet and continuous inkjet technologies.
  • the invention is directed to the manufacture of the emulsion 125 that comprises a bio-active substance such as a pharmaceutical, a neutraceutical, a flavourant and a fragrance.
  • a bio-active substance such as a pharmaceutical, a neutraceutical, a flavourant and a fragrance.
  • the invention is not limited to the manufacture of the emulsion that comprises the bio-active substance.
  • teachings of the present invention are not limited to the use of a single inkjet device that comprises a single inkjet printhead 120.
  • a plurality of inkjet cartridges 110 can be used and an inkjet cartridge 110 can be used with a plurality of inkjet printheads 120.
  • Fig. 1 shows the inkjet cartridge 110 used to generate a droplet jet 130 of a disperse phase of a first immiscible substance 105 that is printed into a container 140 of a continuous phase of the second immiscible substance 115.
  • the droplet jet 130 falls through air the droplet jet 130 generally forms could form a plurality of smaller droplets before coming into contact with a surface of the continuous phase of the second immiscible substance 115.
  • the droplets of the droplet jet 130 emulsify to form the emulsion 125 in the container 140.
  • the droplets can be an oil phase which, when injected into an aqueous phase in the container 140, create an oil-in-water emulsion 125 in the container 140.
  • the droplets can be the aqueous phase which when injected into oil in the container 140 creates a water-in-oil emulsion 125 in the container 140.
  • An emulsifier 135 can be present in the disperse phase of the first immiscible substance 105 in the inkjet cartridge 110 and/or the emulsifier 135 can be present in the continuous phase of the second immiscible substance 115 in the container 140.
  • the bio-active substances are present in the first immiscible substance 115 of the disperse phases which are then spontaneously emulsified into the continuous phase of the second immiscible substance 115.
  • At least one heat exchanger 145, 155, 225 and 265 is present (see also Fig. 1 and Fig.ure 2).
  • the at least one heat exchanger 145, 145b, 225 and 265 is a cooler and a heater.
  • a first heat exchanger 145 can be used to either cool or heat the first immiscible substance 105 and a second heat exchanger 155 can be used to either cool or heat the second immiscible substance 115.
  • the first heat exchanger 145 is inside the inkjet cartridge 110 and can be used to heat or cool the fist im- miscible substance 105.
  • the second heat exchanger 155 is provided inside the container 140 and can be used to heat or cool the second immiscible substance 115 to facilitate the manufacture of the emulsion 125.
  • the temperature of the first heat exchanger 145 and the temperature of the second heat exchanger 155 can be set to a desired temperature depending upon the viscosity of the first immiscible substance 105 and the second immiscible substance 115 and to facilitate the manufacture of the emulsion 125 in the container 140.
  • co-solvents it may be necessary to add co-solvents to either the first immiscible substance 105 and/or the second immiscible substance 115.
  • the use of the co-solvent can reduce the viscosity of the first immiscible substance of the disperse phase 105 and/or the second immis- proficient substance of the continuous phase 115 and therefore provides a sufficient flow rate for the first immiscible substance 105 and/or the second immiscible substance 115 in fluid channels of the apparatus 100, 200.
  • the co-solvents (where used) can be present in either the disperse phase of the first immiscible substance 105 and/or in the continuous phase of the second immiscible substance 115.
  • the fluid channels include all areas of the apparatus 100, 200 as shown in Figures 1 and 2 respectively, that are in contact with any phase of the first immiscible substance of the disperse phase 105 and/or the second immiscible substance of the continuous phase 115 that are used in the manufacture of the emulsion 125.
  • a volatile co-solvent may be necessary to generate a sufficient volume of vapour bubbles.
  • liquids 105 to be used in the inkjet cartridges 110 where the liquids 105 have too large interfacial energy to spontaneously immerse in the continuous phase 115, the addition of co-solvents may be necessary.
  • the emulsifier 135 may be present in either the disperse phase of the first immiscible substance 105 and/or in the continuous phase of the second immiscible substance 115.
  • the invention is used to produce emulsions 125 in a batch system 100.
  • the inkjet cartridge 110 is filled with the disperse phase of the first immiscible substance 105.
  • the disperse phase of the first immiscible substance 105 is then printed as a droplet jet 130, through the inkjet printhead 120 above the container 140 that holds the continuous phase of the second immiscible substance 115.
  • the first immiscible sub- stance 105 immerses spontaneously into the continuous phase of the second immiscible substance 115 to produce the emulsion 125 in the container 140 situated below the inkjet cartridge 110.
  • the emulsion 125 can be made in a continuous preparation that facilitates the manufacture of large quantities of the emul- sion 125.
  • the example of Fig. 2 also enables the manufacture of emulsions that would otherwise be prohibitive due to the immiscible substances having a low volatility (i.e. highly viscous). This is made possible by the fact that such low volatility substances can be thinned with the use of co-solvents and/or heating.
  • the heating is provided by the least one heat exchanger 145, 155, 225 and 265.
  • the at least one heat exchanger 145, 155, 225 and 265 can be used to alter the volatility of the immiscible substances and to provide optimum conditions for the manufacture of the emulsion 125.
  • the co-solvents can then be removed from the emulsion with a dialysis apparatus.
  • the example of Fig. 2 incorporates a collection reservoir 220 for collecting the emulsion 125 as the emulsion 125 is continuously manufactured.
  • the collection reservoir 220 may incorporate a third heat exchanger 225.
  • the third heat exchanger 225 in the collection reservoir 220 is used to either cool or heat the emulsion 125 during manufacture of the emulsion 125.
  • the collection reservoir 220 incorporates an outlet pipe280 and an inlet pipe 281 for the extraction of the prepared emulsion 125.
  • Valves 250 within the apparatus 200 allow the apparatus to be used for the continuous manufacture of the emulsion 125, or for the continuous manufacture of the emulsion 125 that requires the co-solvents which are continuously or later removed.
  • the inkjet cartridge 110 can be refilled in a continuous or noncontinuous manner with the first immiscible substance 105 and/or the emulsifier 135 and/or a co-solvent through the cartridge opening 150. This example is described below in greater detail.
  • the invention is used to produce emulsions 125 in a continuous system 200.
  • the inkjet cartridge 110 is filled with the disperse phase of the first immiscible substance 105.
  • the disperse phase of the first immiscible substance 105 is then printed as a droplet jet 130 through the inkjet printhead 120, into the container 140 of the continuous phase of the second immiscible substance 115.
  • the disperse phase of the first immiscible substance 105 is printed from the inkjet cartridge 110 through the printhead 120 the disperse phase could form a plurality of smaller droplets in the air before the first immiscible substance 105 of the disperse phase immerses into the continuous phase of the second immiscible substance 115 to manufacture the emulsion 125 in the container 140 below.
  • the emulsion 125 is pumped from the container 140 via tubes 210 which connect the container 140 to a collection reservoir 220 using a geared pump 230.
  • the geared pump 230 is operable at a number of different speeds.
  • the geared pump 230 is to be construed as a non-limiting example. Although this disclosure refers to the geared pump 230, any other type of pump may be used alternatively or additionally. Possible forms of other types of pumps may be, but are not limited to a peristaltic or a rotary pump.
  • the geared pump 230 may also be referred to as the pump 230.
  • a co-solvent can be used to lower the viscosity of the immiscible substances 105 and/or 115 used in the manufacture of emulsions 125.
  • the disperse phase of the first immiscible substance 105 together with the possible co-solvents are filled into the inkjet cartridge 110.
  • the dis- perse phase of the first immiscible substance 105 is then printed as a droplet jet 130 through the inkjet printhead 120, into a container 140 of the continuous phase of the second immiscible substance 115.
  • the disperse phase of the first immiscible substance 105 is printed, the disperse phase immerses spontaneously into the continuous phase of the second immiscible substance 115 to manufacture the emulsion 125 in the container 140 be- low.
  • co-solvents in this aspect are not limited to their addition in the disperse phase of the first immiscible substance 105 and the co-solvents can also be added to the continuous phase of the second immiscible substances 115.
  • the co-solvent may need to be removed from the manufactured emulsion 125. This is achieved by having the valves 250 in an open position and allowing the manufactured emulsion 125 to pass through a dialysis apparatus 290.
  • the dialysis apparatus 290 is collectively shown in Fig. 2 to comprise of tubes 210, pumps 230 and a dialysis cartridge 240 which is equipped with a fresh water closed loop at a water reservoir 260.
  • a fourth heat exchanger 265 may be present in the water reservoir 260 of the dialysis apparatus 290.
  • the fourth heat ex- changer 265 in the water reservoir 260 enables the control of the temperature of the water in the water reservoir 260 for the effective removal of the co-solvent from the emulsion 125.
  • the fourth heat exchanger 265 in the water reservoir 260 can be used to either cool or to heat the water in the water reservoir 260.
  • the water reservoir 260 is connected to a wa- ter system by outlet pipe 270 and inlet pipe 271.
  • the temperature of the water reservoir 260 can be pre-set to conduct emulsification at different temperatures to further reduce the volatility of the immiscible substances.
  • the dialysis apparatus 290 is connected to the container 140 and the collection reservoir 220 by a series of tubes 210.
  • the emulsion forming materials are carried through the tubes 210 by a number of pumps 230 through the dialysis apparatus 290 where the co-solvent is removed by dialysis against a membrane (not shown).
  • the manufactured emulsion 125 is then substantially free of co-solvents and is transported to the collection reservoir 220 from the dialysis apparatus 290 via a series of tubes 210 and the pumps 230.
  • the co-solvent remain in the manufactured emulsion 125.
  • the amount of co-solvent that remains in the emulsion 125 can be calculated from the amount of co-solvent that was added to either the first immiscible substance 105 and/or the second immiscible substance 115.
  • Certain amounts of co-solvent remaining in the emulsion 125 are preferable when the emulsion 125 is used as a perfume or as a topological cream.
  • the co-solvents used are usually miscible with either the disperse phase or the continuous phase and are used to reduce the volatility of such substances.
  • the co-solvents do not react with any of the substances used, such as the emulsif ⁇ ers 135 or the first 105 or second immiscible substances 115, or the formed emulsion 125.
  • Fig 3 shows a schematic representation for the method for the manufacture of the emulsion 125 according to the present invention.
  • Start 300 is followed by a step 310 of providing the first immiscible substance 105 which is filled into the inkjet cartridge 110.
  • a next step 315 is to provide the second im- miscible substance 115 in the container 140.
  • This is followed by a step 320 whereby the emulsif ⁇ er 135 is added to either the first immiscible substance of the disperse phase 105 and/ or the second immiscible substance of the continuous phase 115.
  • the emulsions 125 are then printed 330 in the container 140 which contains the second immiscible substance 115 which provides 340 the emulsion 125 ready for collection.
  • Fig. 3 also shows a method for the continuous manufacture of emulsions using inkjet technology according to the schematic in Fig 3.
  • the start 300 is followed by the step 310 of providing of a first immiscible substance of the disperse phase 115 which is filled into the inkjet cartridge 110.
  • the next step 315 is to provide the second immiscible substance of the continuous phase 115 in the container 140.
  • This is followed by the step 320 whereby an emulsif ⁇ er 135 is added to either the first immiscible substance of the disperse phase 105 or the second immiscible substance of the continuous phase 115.
  • the step 350 for the continuous manufacture differs from the batch manufacture process in that, the step 350 is for the addition of the co-solvent to either the first immiscible substance of the disperse phase 105 or the second immiscible substance of the con- tinuous phase 115.
  • the first immiscible substance 105 is then printed in step 345 in the container 140 where the emulsion 125 is manufactured.
  • the emulsion 125 is then withdrawn and subjected to dialysis as in step 360 whereby the co-solvents are removed via the dialysis apparatus 290 from the emulsion 125 to lead to the step of collecting the manufactured emulsion 370.
  • the steps 300 to 370 are then if necessary repeated for the continuous manufacture of the emulsion. It should be noted that this repetition can be used for the manufacture of emulsions 125 without the use of co-solvents for the production of emulsions that contain non volatile first 105 and/or second 115 immiscible substances.
  • the following examples demonstrate the various aspects of the invention but are not intended to limit the invention.
  • the graphs (Figs. 4 - Fig. 29) show a size distribution (for the examples 1 - 21) by intensity (scattered light) of the manufactured emulsion 125, analysed using a Zetasizer Nano series Nano-ZS red label manufactured by Malvern Instruments.
  • Example 1 Preparation of soy bean oil emulsion.
  • Soy bean oil (4.5 g) from Bio Planete and egg lecithin (0.9 g) from Sigma (P5394) were mixed in 24.6 g 2-propanol and stirred until the lecithin is dissolved and a clear yel- Io wish solution was obtained.
  • the solution was filled into the inkjet cartridge 110 and printed as a droplet jet 130 into the container 140 (which in this example a small beaker filled with water).
  • the water is continuously pumped through the apparatus as in Fig 2.
  • the 2-propanol (co- solvent) was constantly removed from the solution in the reservoir 220 utilising cross flow dialysis 290.
  • the whole system is operated as shown in Fig. 2.
  • a sample of the emulsion 125 was filtered through a syringe filter (Schleicher & Sch ⁇ ll FP 30/5.0 CN) with a pore size of 5 ⁇ m into a single use cuvette (Plastibrand, PS; semi micro from Brand) and analysed by dynamic light scattering using a Zetasizer Nano series Nano-ZS red label by Malvern Instruments.
  • a syringe filter Schotasizer Nano series Nano-ZS red label by Malvern Instruments.
  • the emulsion droplets showed a diameter of 264 nm and a relative standard deviation (PDI) of 0.25 as shown in Fig. 4 (Size distribution by intensity of soy bean oil emulsion).
  • the emulsion aggregates in the range of days and showed creaming.
  • the droplets were re-dispersible by simple shaking and showed a similar diameter (258 nm) and size distribution (PDI) of 0.24 as shown in Fig. 5 (Size distribution by intensity of soy bean oil emulsion after 3 weeks)
  • Example 2 Preparation of soy bean oil emulsions in various concentrations.
  • Soy bean oil from Bio Planete and egg lecithin (3% by weight) from Sigma (P5394) were mixed in 2-propanol and stirred until the lecithin was dissolved and a clear yellowish solution was obtained.
  • Example 3 Soy bean oil and sodium dodecyl sulphate (SDS) in various concentrations.
  • Soy bean oil (5-15% by weight) from Bio Planete was mixed in 2-propanol and stirred until a clear yellowish solution was obtained.
  • Sodium dodecyl sulphate (SDS) (3% by weight) from Roth was dissolved in water and the printing process described in Example 1 was started using the sodium dodecyl sulphate (SDS) in water solution instead of pure water.
  • Example 4 Soy bean oil and other surfactants.
  • Soy bean oil (15% by weight) from Bio Planete was mixed in 2-propanol and stirred until the lecithin extract was dissolved and a clear yellowish solution was obtained.
  • a surfactant sodium dodecyl sulphate (SDS), sodium laureth sulfate (SLES), sodium do- decylbenzene sulfonate (SDBS), egg lecithin (PC), cosmetic emulsif ⁇ er "LV41", disodium- cocoylglutamate, cetyltrimethylammonium bromide (CTAB), sodium cocoamphoacetate, polyethylene glycol sorbitan monooleate (T ween 80), polyethylene glycol octylphenol ether (Triton X-100) and poly ethoxylated fatty alcohol (Dehydol LT7), 3% by weight) is dissolved in water and the printing process as described in Example 3 was started.
  • SDS sodium dodecyl sulphate
  • SLES sodium la
  • SDS sodium dodecyl sulfate
  • SLES sodium laureth sulfate
  • SDBS sodium dodecyl benzene sulfonate
  • Example 5 Soy bean oil and lecithin at various temperatures.
  • Soy bean oil (15% by weight) from Bio Planete and egg lecithin (3% by weight) from Sigma (P5394) were mixed in 2-propanol and stirred until the lecithin is dissolved and a clear yellowish solution was obtained.
  • the temperature of the water in the closed loop is set to various temperatures ranging from 6 0 C to 45 0 C.
  • Example 6 Various oils and lecithin.
  • Example 7 Fragrances in oil emulsions.
  • Soy bean oil (15% by weight) from Bio Planete, a fragrance oil/ingredient (orange, ylang-ylang, carnation, coriander, bergamotte, menthol, each 1% by weight) and egg lecithin (3% by weight) from Sigma (P5394) was mixed in 2-propanol and stirred until the lecithin is dissolved and a clear yellowish solution was obtained.
  • flavoured emulsions were studied in preparations similar to Ex- ample 7.
  • Soy bean oil (15% by weight) from Bio Planete, a flavour oil/ingredient (orange, carnation, coriander, bergamotte, menthol, cayenne pepper extract, peppermint, each 1% by weight) and egg lecithin (3% by weight) from Sigma (P5394) was mixed in 2-propanol and stirred until the lecithin is dissolved and a clear yellowish solution was obtained.
  • a flavour oil/ingredient range, carnation, coriander, bergamotte, menthol, cayenne pepper extract, peppermint, each 1% by weight
  • egg lecithin 3% by weight
  • Example 9 Active ingredients in oil emulsions.
  • Soy bean oil (15% by weight) from Bio Planete, an active ingredient (tocopherol (Vitamin E), cod liver oil, clotrimazol (Antifungal medicament), piroxicam (on steroidal anti inflammatory drug), each 1% by weight) and egg lecithin (3% by weight) from Sigma (P5394) were mixed in 2-propanol and stirred until the lecithin was dissolved and a clear yellowish solution was obtained.
  • an active ingredient tocopherol (Vitamin E)
  • cod liver oil cod liver oil
  • clotrimazol Antifungal medicament
  • piroxicam on steroidal anti inflammatory drug
  • Example 10 Paraffin oil emulsions.
  • Paraffin oil (2-15% by weight) from Caelo was mixed in tetrahydrofuran (THF) and a clear solution was obtained.
  • Sodium dodecyl sulphate (SDS) (3% by weight) from Roth is dissolved in water and the printing process described in Example 1 is started using the sodium dodecyl sulphate (SDS) in water solution.
  • Example 11 Paraffin oil emulsions.
  • Paraffin oil (15% by weight) from Caelo was mixed in tetrahydrofuran (THF) and a clear solution was obtained.
  • a surfactant sodium dodecyl sulphate (SDS), sodium dodecyl benzene sulphonate (SDBS), sodium laureth sulphate (SLES) , Plantaren APG 1200, each 3% by weight
  • SDS sodium dodecyl sulphate
  • SDBS sodium dodecyl benzene sulphonate
  • SLES sodium laureth sulphate
  • Example 12 Paraffin oil emulsions.
  • Paraffin oil (5% by weight) from Caelo was mixed in tetrahydrofurane (THF) and a clear solution was obtained.
  • a surfactant sodium dodecyl sulphate (SDS), sodium dodecyl benzene sulphonate (SDBS), sodium laureth sulphate (SLES)
  • SDS sodium dodecyl sulphate
  • SDBS sodium dodecyl benzene sulphonate
  • SLES sodium laureth sulphate
  • Example 13 Castor oil - lecithin in various solvents.
  • the influence of the type of the solvent was studied in preparations similar to Example 1.
  • Soy bean oil (15% by weight) and egg lecithin (3% by weight) from Sigma (P5394) are mixed in various solvents (2-propanol, ethanol and tetrahydrofuran (THF) and stirred until the lecithin was dissolved and a clear yellowish solution was obtained.
  • Example 14 Influence of number of printers.
  • Soy bean oil (15% by weight) and egg lecithin (3% by weight) from Sigma (P5394) are mixed in 2-propanol and stirred until the lecithin was dissolved and a clear yellowish solution was obtained.
  • Example 15 Influence of type of printer cartridge.
  • the influence of the model of the printer was studied in preparations similar to Example 1.
  • Soy bean oil (15% by weight) and egg lecithin (3% by weight) from Sigma (P5394) are mixed in 2-propanol and stirred until the lecithin was dissolved and a clear yellowish solution was obtained.
  • Example 16 Influence of shape of container.
  • Soy bean oil (15% by weight) and egg lecithin (3% by weight) from Sigma (P5394) are mixed in 2-propanol and stirred until the lecithin was dissolved and a clear yellowish solution was obtained.
  • Example 17 influence of pumping speed.
  • Soy bean oil (15% by weight) and egg lecithin (3% by weight) from Sigma (P5394) are mixed in 2-propanol and stirred until the lecithin was dissolved and a clear yellowish solution was obtained.
  • Fig. 25 Size distribution by intensity of soy bean oil (15%) emulsion stabilised by lecithin
  • Example 18 influence of point of time of dialysis.
  • the influence of the point of time of the solvent dialysis was studied in preparations similar to Example 1.
  • Soy bean oil (15% by weight) and egg lecithin (3% by weight) from Sigma (P5394) are mixed in 2-propanol and stirred until the lecithin was dissolved and a clear yellowish solution was obtained.
  • the dialysis was operated during the preparation of the emulsion and after the completion of the preparation.
  • Soy bean oil (15% by weight) and egg lecithin (3% by weight) from Sigma (P5394) are mixed in 2-propanol and stirred until the lecithin was dissolved and a clear yellowish solution was obtained.
  • the preparation was operated using thermal inkjet printers (HP 2000C) and piezo inkjet printers (EPSON StylusColor 300).
  • Soy bean oil (15% by weight) and egg lecithin (3% by weight) from Sigma (P5394) were mixed in 2-propanol and stirred until the lecithin was dissolved and a clear yellowish solution was obtained.
  • soy bean oil was equipped with a trace of the dye Sudan IV in one case.
  • Example 21 preparation of a water in oil emulsion

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  • Chemical & Material Sciences (AREA)
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  • Colloid Chemistry (AREA)
  • Medicinal Preparation (AREA)

Abstract

A method and an apparatus for the manufacture of an emulsion (125) using an inkjet cartridge (110). A first immiscible substance (105) is printed as a droplet jet (130) from the inkjet cartridge (110) into a second immiscible substance (115) which is below an inkjet printhead (120) of the inkjet cartridge (110). The emulsion (125) is manufactured in a container (140) which contains the second immiscible substance (115).

Description

Description
Title: InkJet Printer for the Manufacture of Emulsions
Field of Invention
[0001] The present invention discloses a method for the manufacture of an emulsion using an inkjet device.
Prior Art
[0002] The use of inkjet devices in industrial applications is known in the literature.
[0003] US Patent No. US 6123861 is titled "Fabrication of microchip drug delivery devices" (inventors John T Santini, Michael J Cima and S. Langer) The US Patent No. US 6123861 is assigned to Massachusetts Institute of Technology, Cambridge Mass. USA. The US 6123861 document teaches fabrication methods of microchips that control both the rate and time of release of multiple chemical substances used in the pharmaceutical indus- try and allow for the release of a wide variety of molecules in either a continuous or pulsatile manner. A release system, which includes the molecules to be delivered, is inserted into reservoirs by injection, inkjet printing, or spin coating methods. The US 6123861 document exemplifies the use of medicinal compounds and their use within inkjet technology. The US 6123861 patent is directed to the efficacy of drug administration.
[0004] US Patent publication No. 2004/0181196 is titled "Cutaneous administration system". The US 2004/0181196 document (inventors Ray L Pickup, Clement C Lo and William D Noonan) is assigned to The Hewlett-Packard Company, USA. This US 2004/0181196 document describes the cutaneous administration of bio-active agents by a jet dispenser using inkjet technology. The jet dispenser propels precise volumes of the bio- active agent towards the skin, where the bio-active agents exert their effect. [0005] International Patent application No. WO2006/044695 is titled "InkJet dispenser for automated drug administration in a hospital management system" (inventors Vitello C. John, Welkley Steve, Evans Andrew and Greeven John). The WO 2006/044695 document also describes the cutaneous administration of bio-active agents by a jet dispenser using inkjet technology. The inkjet dispenser propels precise volumes of a bio-active agent towards the skin, where the bio-active agents exert their effect.
[0006] An article in Small 2005, 1, No.12, 1177-1180; which is titled "Direct preparation and loading of lipid and polymer vesicles using inkjets" by Stephan Hauschild, et al. This document discloses the direct preparation of nanometre sized, unilamellar lipid and polymer vesicles with a narrow size distribution using inkjet printers. The size of the vesicles can be controlled via the amphiphiles concentration and the cartridge type.
[0007] An article in Forensics and Homeland Security by Fletcher is viewable at the URL http://www.cstl.nist.gov/projects/fy06/fhls0683703.pdf and is titled "Production of Polymer Test Particle Standards by InkJet Printing". The Fletcher article discloses a method for the manufacture of microspheres that are mono-disperse polymer particles by using a "sphere-jet" system. The "sphere-jet" system is a drop on demand inkjet printer with a piezoelectric driven tip consisting of a micro capillary with a 50 μm orifice diameter. The inkjet printer of Fletcher is submerged under water and is used to extrude a polymer- analyte solution. The particle size is controlled by the concentration of the polymer, fluid feed rate and the applied frequency. The mono-disperse polymer particles are manufactured by an oil- water emulsion reaction.
[0006] None of the prior art discloses a method for the manufacture of the emulsion prepared using inkjet devices according to the present invention.
Background of Invention
[0007] An emulsion is a mixture of two immiscible or unblendable substances. Emulsions are part of a more general class of two-phase systems of matter called colloids. The term colloid and emulsion are sometimes used interchangeably, the term emulsion tends to im- ply that both a dispersed phase of the emulsion and a continuous phase of the emulsion are a liquid.
[0008] An emulsifϊer (also known as an emulgent or surfactant) is a substance which stabi- uses an emulsion. An example of food emulsifiers are egg yolk (where the main emulsifying chemical is the phospholipid lecithin) and mustard where a variety of chemicals in the mucilage surrounding the seed hull act as the emulsifϊer; proteins and low-molecular weight emulsifiers are also common. Particles can also stabilise the emulsion through a mechanism called Pickering stabilization. Detergents are another class of emulsifier that will chemically interact with both oil and water, stabilising the interface between the oil or water droplets in the emulsion. This principle is exploited in soap to remove grease for the purpose of cleaning.
[0009] Examples of emulsions include milk (fat dispersed in water), butter (water dis- persed in fat), mayonnaise (oil dispersed in water which is stabilised with the emulsifier lecithin) and ice-cream (fat in water which is then frozen). A huge number of emulsions exist in the cosmetic and pharmaceutical industry, such as creams, lotions and ointments. Emulsions are also used as drug delivery systems such as Propofol which is a liquid anaesthetic dissolved in oil.
[00010] Emulsions are conventionally manufactured by the shear- induced break-up of macroscopic liquid droplets of a disperse phase into a continuous phase. The shear is provided by mechanical methods such as shaking, stirring, homogenising or ultrasound.
[00011] Emulsions are generally unstable and thus do not form spontaneously. Generally for the manufacture of most emulsions, high shear forces are needed with a corresponding intake of a large amount of energy to either the disperse phase or the continuous phase of the manufactured emulsion. The energy intake by the emulsion usually results in a considerable amount of damage to the immiscible substances used to manufacture the emulsion or to damage to the manufactured emulsion itself. Such damage can be mechanical damage and may lead to denaturisation of bio-molecules, cleavage damage of chemical compounds or the damage can be due to a result of an increase in temperature within the immiscible substances due to the energy intake in the emulsion manufacturing process.
[00012] Therefore conventional methods for the manufacture of the emulsion are prohibi- tive where the emulsion consists of a sensitive bio -active component such as pharmaceuticals, neutraceuticals, bio-active compounds, flavourants or fragrances.
[00013] InkJet cartridges provide a means to generate very small substance droplets. The droplet volumes can be down to picolitres (10~12 litres). A jet of droplets from an inkjet cartridge can be injected into a liquid to produce emulsions with dispersed droplets which have diameters in a typical range of 10 - 500 nm.
[00014] A method for the manufacture of the emulsion using the inkjet cartridge avoids the use of the harsh mechanical methods outlined above. The method for the manufacture of emulsions using the inkjet cartridge provides a means to manufacture the emulsion that contains sensitive compounds in a gentle environment, such that the sensitive compounds are not damaged by conventional emulsion manufacturing methods.
Summary of Invention
[00015] The present invention teaches a method and an apparatus for the manufacture of an emulsion, preferably but not limited to the emulsion containing a bio-active substance.
[00016] The method comprises providing a first immiscible substance of the bio-active substance in at least one inkjet cartridge and providing a second immiscible substance in a container. An emulsifϊer may be present in the inkjet cartridge and/or in the container. The first immiscible substance is printed through an inkjet printhead which is located above the surface of the second immiscible substance. The first immiscible substance emerges as a droplet jet from the inkjet printhead into the container where the second immiscible sub- stance is present. The first immiscible substance forms the emulsion with the second immiscible substance in the container. [00017] The method allows for the manufacture of the emulsion at various temperatures. The ability to control the temperature of either the first immiscible substance and/or the second immiscible substance is used to alter the viscosity of either first immiscible substance and/or the second immiscible substance during the manufacture of the emulsion.
[00018] The method allows for the manufacture of a wide range of emulsions that would usually prove problematic. The invention allows for the use of co-solvents. The co-solvents are used to reduce the viscosity of the immiscible substances and also allows the preparation of emulsions at various temperatures to aid the manufacture of the emulsions. Where co-solvents can be used, they are removed from the manufactured emulsion by a dialysis or other techniques such as rectification, adsorption or stripping.
[00019] The invention provides for the manufacture of emulsions without affecting the chemical properties of either the first immiscible substance or the second immiscible sub- stance. For example, the method and the apparatus allow for the manufacture of bio-active emulsions efficiently, quickly and in large quantities without affecting their chemical properties.
[00020] The invention provides for the continuous manufacture of the emulsion allowing large quantities of the emulsion to be manufactured, which may not be have been previously possible by using co-solvents, warming means and dialysis for the manufacture of the emulsion.
Description of Drawings
[00021] Figure 1. Depicts the manufacture of emulsions using inkjet devices in a batch preparation system.
[00022] Figure 2. Depicts the manufacture of emulsions using inkjet devices in a continu- ous flow system. [00023] Figure 3. Depicts a schematic flow diagram for the manufacture of emulsions using inkjet devices.
[00024] Figure 4. Shows a size distribution by intensity of soy bean oil (A) emulsion.
[00025] Figure 5. Shows a size distribution by intensity of soy bean oil (A) emulsion after 3 weeks.
[00026] Figure 6. Shows a size distribution by intensity of soy bean oil emulsions with various concentrations (15% - A, 3% - B, 1% - C, all concentrations in % by weight) of soy bean oil in the cartridge/printhead.
[00027] Figure 7. Shows a size distribution by intensity of soy bean oil (15%) emulsion stabilised by sodium dodecyl sulphate (SDS) after preparation (A) and after 5 weeks (B).
[00028] Figure 8. Shows a size distribution by intensity of soy bean oil (5%) emulsion stabilised by sodium dodecyl sulphate (SDS) after preparation (A) and after 5 weeks (B).
[00029] Figure 9. Shows a size distribution by intensity of soy bean oil (15%) emulsion stabilised with various surfactants, sodium dodecyl sulphate (SDS) (A), egg lecithine (B) and cetyltrimethylammonium bromide (CTAB) (C) (each 3%) - after preparation.
[00030] Figure 10. Shows a size distribution by intensity of soy bean oil (15%) emulsion stabilised by sodium dodecyl sulphate (SDS) (A), sodium laureth sulphate (SLES) (B) and sodium dodecyl benzene sulphonate (SDBS) (C) (each 3%) after preparation.
[00031] Figure 11. Shows a size distribution by intensity of soy bean oil (15%) emulsion stabilised with various surfactants, sodium dodecyl sulphate (SDS) (A), sodium laureth sulphate (SLES) (B) and sodium dodecyl benzene sulphonate (SDBS) (C) (each 3%) - after 3-5 weeks. [00032] Figure 12. Shows a size distribution by intensity of soy bean oil (15%) emulsion at various temperatures, stabilised by lecithin (3%) at 6 0C (A), 15 0C (B) and 35 0C (C) - after preparation.
[00033] Figure 13. Shows a size distribution by intensity of soy bean oil (15%) emulsion at various temperatures stabilised by lecithin (3%) at 6 0C (A), 15 0C (B) and 35 0C (C) - 3-5 weeks after preparation.
[00034] Figure 14. Shows a size distribution by intensity of various oil emulsions, of lin- seed oil (A), sweet almond oil (B) and fish oil (C) (each 15%) - stabilised by lecithin (3%) after preparation.
[00035] Figure 15. Shows a size distribution by intensity of various oils - (15%) stabilised by lecithin (each 3%) and equipped with coriander oil (A), orange oil (B) and menthol (C) ( 1 %) after preparation.
[00036] Figure 16. Shows a size distribution by intensity of fragrant emulsions of soy bean oil (15%) stabilised by lecithin (3%) and equipped with coriander oil (A), carnation oil (B) and cayenne pepper extract (C) (each 1%) after preparation.
[00037] Figure 17. Shows a size distribution by intensity of emulsions containing various active ingredients with soy bean oil (15%) stabilised by lecithin (3%) equipped with tocopherol (A), clotrimazol (B) and piroxicam (C) - (each 1%) after preparation.
[00038] Figure 18. Shows size distribution by intensity of emulsions with concentrations of 15% (A), 5% (B) and 2% (C) of paraffin oil in the cartridge stabilised by sodium dode- cyl sulphate (SDS) (3%) after preparation
[00039] Figure 19. Shows a size distribution by intensity of paraffin oil (15%) emulsion stabilised by - sodium dodecyl sulphate (SDS) (A), sodium dodecyl benzene sulphate (SDBS) (B) and sodium laureth sulphate (SLES) (C) (3%) after preparation. [00040] Figure 20. Shows a size distribution by intensity of paraffin oil (5%) emulsion stabilised by - sodium dodecyl sulphate (SDS) with concentrations of 3% (A) and 5% (B) after preparation.
[00041] Figure 21. Shows a size distribution by intensity of oil (15%) emulsion stabilised by lecithin (3%) printed from 2-propanol (A), ethanol (B) and tetrahydrofuran (THF) (C).
[00042] Figure 22. Shows a size distribution by intensity of soy bean oil (15%) emulsion stabilised by lecithin (3%) printed from one printer (A) and two printers (B).
[00043] Figure 23. Shows a size distribution by intensity of soy bean oil (15%) emulsion stabilised by lecithin (3%) printed from printer model #1 (A) and printer model #2 (B).
[00044] Figure 24. Shows a size distribution by intensity of soy bean oil (15%) emulsion stabilised by lecithin (3%) printed into various shapes of container, shape #1 (A), shape #2 (B) and shape #3(C).
[00045] Figure 25. Shows a size distribution by intensity of soy bean oil (15%) emulsion stabilised by lecithin (3%) printed in water under various pump speeds, speed #1 (A), speed #2 (B) and speed #3 (C) of the first closed loop.
[00046] Figure 26. Shows a size distribution by intensity of soy bean oil (15%) emulsion stabilised by lecithin (3%) printed in water under co-solvent removal continuously during preparation (A) and after preparation (B) via dialysis apparatus.
[00047] Figure 27. Shows a size distribution by intensity of soy bean oil (15%) emulsion stabilised by lecithin (3%) printed in water using thermal inkjet printers (#1, A and #2, B) and piezo inkjet (C) printers.
[00048] Figure 28. Shows a size distribution by intensity of soy bean oil (15%) emulsion stabilised by lecithin (3%) printed in water equipped with dye Sudan IV (A) and without dye (B). [00049] Figure 29. Shows a size distribution by intensity of water in oil emulsion stabilised by polyethylene glycol octylphenol ether (Triton X-IOO) printed in paraffin oil (A).
Detailed Description
[00050] The present invention teaches a method 300 and an apparatus 100, 200 for the manufacture of an emulsion 125 utilising an inkjet cartridge 110. The inkjet cartridge 110 is preferably a thermal inkjet cartridge. The inkjet printhead 120 is preferably a thermal inkjet printhead. The invention is, however, not limited to a particular inkjet technology and incorporates all such known technologies such as thermal inkjet, piezoelectric inkjet, (solenoid) valve inkjet and continuous inkjet technologies.
[00051] The invention is directed to the manufacture of the emulsion 125 that comprises a bio-active substance such as a pharmaceutical, a neutraceutical, a flavourant and a fragrance. The invention is not limited to the manufacture of the emulsion that comprises the bio-active substance.
[00052] The teachings of the present invention are not limited to the use of a single inkjet device that comprises a single inkjet printhead 120. A plurality of inkjet cartridges 110 can be used and an inkjet cartridge 110 can be used with a plurality of inkjet printheads 120.
[00053] Fig. 1 shows the inkjet cartridge 110 used to generate a droplet jet 130 of a disperse phase of a first immiscible substance 105 that is printed into a container 140 of a continuous phase of the second immiscible substance 115. As the droplet jet 130 falls through air the droplet jet 130 generally forms could form a plurality of smaller droplets before coming into contact with a surface of the continuous phase of the second immiscible substance 115. The droplets of the droplet jet 130 emulsify to form the emulsion 125 in the container 140. The droplets can be an oil phase which, when injected into an aqueous phase in the container 140, create an oil-in-water emulsion 125 in the container 140. The droplets can be the aqueous phase which when injected into oil in the container 140 creates a water-in-oil emulsion 125 in the container 140. [00054] An emulsifier 135 can be present in the disperse phase of the first immiscible substance 105 in the inkjet cartridge 110 and/or the emulsifier 135 can be present in the continuous phase of the second immiscible substance 115 in the container 140. In one aspect of the invention, the bio-active substances are present in the first immiscible substance 115 of the disperse phases which are then spontaneously emulsified into the continuous phase of the second immiscible substance 115.
[00055] To facilitate the manufacture of the emulsion at least one heat exchanger 145, 155, 225 and 265 is present (see also Fig. 1 and Fig.ure 2). The at least one heat exchanger 145, 145b, 225 and 265 is a cooler and a heater. A first heat exchanger 145 can be used to either cool or heat the first immiscible substance 105 and a second heat exchanger 155 can be used to either cool or heat the second immiscible substance 115. The first heat exchanger 145 is inside the inkjet cartridge 110 and can be used to heat or cool the fist im- miscible substance 105. The second heat exchanger 155 is provided inside the container 140 and can be used to heat or cool the second immiscible substance 115 to facilitate the manufacture of the emulsion 125. The temperature of the first heat exchanger 145 and the temperature of the second heat exchanger 155 can be set to a desired temperature depending upon the viscosity of the first immiscible substance 105 and the second immiscible substance 115 and to facilitate the manufacture of the emulsion 125 in the container 140.
[00056] It may be necessary to add co-solvents to either the first immiscible substance 105 and/or the second immiscible substance 115. The use of the co-solvent can reduce the viscosity of the first immiscible substance of the disperse phase 105 and/or the second immis- cible substance of the continuous phase 115 and therefore provides a sufficient flow rate for the first immiscible substance 105 and/or the second immiscible substance 115 in fluid channels of the apparatus 100, 200. The co-solvents (where used) can be present in either the disperse phase of the first immiscible substance 105 and/or in the continuous phase of the second immiscible substance 115. The fluid channels include all areas of the apparatus 100, 200 as shown in Figures 1 and 2 respectively, that are in contact with any phase of the first immiscible substance of the disperse phase 105 and/or the second immiscible substance of the continuous phase 115 that are used in the manufacture of the emulsion 125. [00057] For liquids 105 to be used in the inkjet cartridge 110 based on a thermal inkjet cartridge 110, the addition of a volatile co-solvent may be necessary to generate a sufficient volume of vapour bubbles.
[00058] For liquids 105 to be used in the inkjet cartridges 110, where the liquids 105 have too large interfacial energy to spontaneously immerse in the continuous phase 115, the addition of co-solvents may be necessary.
[00059] The emulsifier 135 may be present in either the disperse phase of the first immiscible substance 105 and/or in the continuous phase of the second immiscible substance 115.
[00060] In one aspect of the invention, the invention is used to produce emulsions 125 in a batch system 100. In this aspect the inkjet cartridge 110 is filled with the disperse phase of the first immiscible substance 105. The disperse phase of the first immiscible substance 105 is then printed as a droplet jet 130, through the inkjet printhead 120 above the container 140 that holds the continuous phase of the second immiscible substance 115. As the disperse phase of the first immiscible substance 105 is printed, the first immiscible sub- stance 105 immerses spontaneously into the continuous phase of the second immiscible substance 115 to produce the emulsion 125 in the container 140 situated below the inkjet cartridge 110.
[00061] As the disperse phase of the first immiscible substance 105 immerses into the con- tinuous phase of the second immiscible substance 115 the mixture is agitated in the container 140 to promote the manufacture of the emulsion 125.
[00062] In a further aspect of the invention shown in Fig. 2, the emulsion 125 can be made in a continuous preparation that facilitates the manufacture of large quantities of the emul- sion 125. The example of Fig. 2 also enables the manufacture of emulsions that would otherwise be prohibitive due to the immiscible substances having a low volatility (i.e. highly viscous). This is made possible by the fact that such low volatility substances can be thinned with the use of co-solvents and/or heating. The heating is provided by the least one heat exchanger 145, 155, 225 and 265. The at least one heat exchanger 145, 155, 225 and 265 can be used to alter the volatility of the immiscible substances and to provide optimum conditions for the manufacture of the emulsion 125. The co-solvents can then be removed from the emulsion with a dialysis apparatus. The example of Fig. 2 incorporates a collection reservoir 220 for collecting the emulsion 125 as the emulsion 125 is continuously manufactured. The collection reservoir 220 may incorporate a third heat exchanger 225. The third heat exchanger 225 in the collection reservoir 220 is used to either cool or heat the emulsion 125 during manufacture of the emulsion 125. The collection reservoir 220 incorporates an outlet pipe280 and an inlet pipe 281 for the extraction of the prepared emulsion 125. Valves 250 within the apparatus 200 allow the apparatus to be used for the continuous manufacture of the emulsion 125, or for the continuous manufacture of the emulsion 125 that requires the co-solvents which are continuously or later removed. For the manufacture of larger amounts of the emulsion 125, the inkjet cartridge 110 can be refilled in a continuous or noncontinuous manner with the first immiscible substance 105 and/or the emulsifier 135 and/or a co-solvent through the cartridge opening 150. This example is described below in greater detail.
[00063] In this aspect of the invention, the invention is used to produce emulsions 125 in a continuous system 200. In this aspect the inkjet cartridge 110 is filled with the disperse phase of the first immiscible substance 105. The disperse phase of the first immiscible substance 105 is then printed as a droplet jet 130 through the inkjet printhead 120, into the container 140 of the continuous phase of the second immiscible substance 115. As the disperse phase of the first immiscible substance 105 is printed from the inkjet cartridge 110 through the printhead 120 the disperse phase could form a plurality of smaller droplets in the air before the first immiscible substance 105 of the disperse phase immerses into the continuous phase of the second immiscible substance 115 to manufacture the emulsion 125 in the container 140 below.
[00064] As the disperse phase of the first immiscible substance 105 immerses into the continuous phase of the second immiscible substance 115 the mixture is agitated in the container 140 to promote manufacture of the emulsion 125. [00065] As the emulsion 125 is manufactured, the emulsion 125 is pumped from the container 140 via tubes 210 which connect the container 140 to a collection reservoir 220 using a geared pump 230. The geared pump 230 is operable at a number of different speeds. The geared pump 230 is to be construed as a non-limiting example. Although this disclosure refers to the geared pump 230, any other type of pump may be used alternatively or additionally. Possible forms of other types of pumps may be, but are not limited to a peristaltic or a rotary pump. The geared pump 230 may also be referred to as the pump 230.
[00066] In a further aspect of the invention where the invention is used for the continuous manufacture of emulsions 125, a co-solvent can be used to lower the viscosity of the immiscible substances 105 and/or 115 used in the manufacture of emulsions 125. In continuous preparations of the emulsion 125 the disperse phase of the first immiscible substance 105 together with the possible co-solvents are filled into the inkjet cartridge 110. The dis- perse phase of the first immiscible substance 105 is then printed as a droplet jet 130 through the inkjet printhead 120, into a container 140 of the continuous phase of the second immiscible substance 115. As the disperse phase of the first immiscible substance 105 is printed, the disperse phase immerses spontaneously into the continuous phase of the second immiscible substance 115 to manufacture the emulsion 125 in the container 140 be- low.
[00067] The use of co-solvents in this aspect are not limited to their addition in the disperse phase of the first immiscible substance 105 and the co-solvents can also be added to the continuous phase of the second immiscible substances 115.
[00068] Where a co-solvent is used, the co-solvent may need to be removed from the manufactured emulsion 125. This is achieved by having the valves 250 in an open position and allowing the manufactured emulsion 125 to pass through a dialysis apparatus 290. The dialysis apparatus 290 is collectively shown in Fig. 2 to comprise of tubes 210, pumps 230 and a dialysis cartridge 240 which is equipped with a fresh water closed loop at a water reservoir 260. In a further aspect of the present invention a fourth heat exchanger 265 may be present in the water reservoir 260 of the dialysis apparatus 290. The fourth heat ex- changer 265 in the water reservoir 260 enables the control of the temperature of the water in the water reservoir 260 for the effective removal of the co-solvent from the emulsion 125. The fourth heat exchanger 265 in the water reservoir 260 can be used to either cool or to heat the water in the water reservoir 260. The water reservoir 260 is connected to a wa- ter system by outlet pipe 270 and inlet pipe 271. The temperature of the water reservoir 260 can be pre-set to conduct emulsification at different temperatures to further reduce the volatility of the immiscible substances. The dialysis apparatus 290 is connected to the container 140 and the collection reservoir 220 by a series of tubes 210. The emulsion forming materials are carried through the tubes 210 by a number of pumps 230 through the dialysis apparatus 290 where the co-solvent is removed by dialysis against a membrane (not shown). The manufactured emulsion 125 is then substantially free of co-solvents and is transported to the collection reservoir 220 from the dialysis apparatus 290 via a series of tubes 210 and the pumps 230.
[00069] In a further aspect of the present invention it is preferable that certain amounts of the co-solvent remain in the manufactured emulsion 125. The amount of co-solvent that remains in the emulsion 125 can be calculated from the amount of co-solvent that was added to either the first immiscible substance 105 and/or the second immiscible substance 115. Certain amounts of co-solvent remaining in the emulsion 125 are preferable when the emulsion 125 is used as a perfume or as a topological cream.
[00070] The co-solvents used are usually miscible with either the disperse phase or the continuous phase and are used to reduce the volatility of such substances. The co-solvents do not react with any of the substances used, such as the emulsifϊers 135 or the first 105 or second immiscible substances 115, or the formed emulsion 125.
[00071] The aspects of the invention are described in more detail with reference to Fig. 3. Fig 3 shows a schematic representation for the method for the manufacture of the emulsion 125 according to the present invention.
[00072] Start 300 is followed by a step 310 of providing the first immiscible substance 105 which is filled into the inkjet cartridge 110. A next step 315 is to provide the second im- miscible substance 115 in the container 140. This is followed by a step 320 whereby the emulsifϊer 135 is added to either the first immiscible substance of the disperse phase 105 and/ or the second immiscible substance of the continuous phase 115.
[00073] In a method for the batch manufacture of emulsions 125, the emulsions 125 are then printed 330 in the container 140 which contains the second immiscible substance 115 which provides 340 the emulsion 125 ready for collection.
[00074] Fig. 3 also shows a method for the continuous manufacture of emulsions using inkjet technology according to the schematic in Fig 3. The start 300 is followed by the step 310 of providing of a first immiscible substance of the disperse phase 115 which is filled into the inkjet cartridge 110. The next step 315 is to provide the second immiscible substance of the continuous phase 115 in the container 140. This is followed by the step 320 whereby an emulsifϊer 135 is added to either the first immiscible substance of the disperse phase 105 or the second immiscible substance of the continuous phase 115.
[00075] The step 350 for the continuous manufacture differs from the batch manufacture process in that, the step 350 is for the addition of the co-solvent to either the first immiscible substance of the disperse phase 105 or the second immiscible substance of the con- tinuous phase 115. The first immiscible substance 105 is then printed in step 345 in the container 140 where the emulsion 125 is manufactured. The emulsion 125 is then withdrawn and subjected to dialysis as in step 360 whereby the co-solvents are removed via the dialysis apparatus 290 from the emulsion 125 to lead to the step of collecting the manufactured emulsion 370. The steps 300 to 370 are then if necessary repeated for the continuous manufacture of the emulsion. It should be noted that this repetition can be used for the manufacture of emulsions 125 without the use of co-solvents for the production of emulsions that contain non volatile first 105 and/or second 115 immiscible substances.
Examples
[00076] The following examples demonstrate the various aspects of the invention but are not intended to limit the invention. [00077] The graphs (Figs. 4 - Fig. 29) show a size distribution (for the examples 1 - 21) by intensity (scattered light) of the manufactured emulsion 125, analysed using a Zetasizer Nano series Nano-ZS red label manufactured by Malvern Instruments.
[00078] Example 1 - Preparation of soy bean oil emulsion.
[00079] Soy bean oil (4.5 g) from Bio Planete and egg lecithin (0.9 g) from Sigma (P5394) were mixed in 24.6 g 2-propanol and stirred until the lecithin is dissolved and a clear yel- Io wish solution was obtained.
[00080] The solution was filled into the inkjet cartridge 110 and printed as a droplet jet 130 into the container 140 (which in this example a small beaker filled with water). The water is continuously pumped through the apparatus as in Fig 2. The 2-propanol (co- solvent) was constantly removed from the solution in the reservoir 220 utilising cross flow dialysis 290. The whole system is operated as shown in Fig. 2.
[00081] After the solution was printed into water the 2-propanol (co-solvent) was removed by dialysis to yield an opaque slightly yellowish emulsion 125.
[00082] A sample of the emulsion 125 was filtered through a syringe filter (Schleicher & Schϋll FP 30/5.0 CN) with a pore size of 5 μm into a single use cuvette (Plastibrand, PS; semi micro from Brand) and analysed by dynamic light scattering using a Zetasizer Nano series Nano-ZS red label by Malvern Instruments.
[00083] The emulsion droplets showed a diameter of 264 nm and a relative standard deviation (PDI) of 0.25 as shown in Fig. 4 (Size distribution by intensity of soy bean oil emulsion). The emulsion aggregates in the range of days and showed creaming. The droplets were re-dispersible by simple shaking and showed a similar diameter (258 nm) and size distribution (PDI) of 0.24 as shown in Fig. 5 (Size distribution by intensity of soy bean oil emulsion after 3 weeks) [00084] Example 2 - Preparation of soy bean oil emulsions in various concentrations.
[00085] The influence of the oil concentration was studied in preparations similar to Example 1.
[00086] Soy bean oil from Bio Planete and egg lecithin (3% by weight) from Sigma (P5394) were mixed in 2-propanol and stirred until the lecithin was dissolved and a clear yellowish solution was obtained.
[00087] In every case an opaque and slightly yellowish emulsion was obtained after the preparation. Analysis by dynamic light scattering showed similar results to example 1. The diameter ranges from 193 nm to 261 nm (PDI 0.24 to 0.29), as shown in Fig 6 Size distribution by intensity of soy bean oil emulsions with various concentrations (15% - A, 3% - B, 1% - C) of soy bean oil in the cartridge.. Other soy bean oil concentrations other than those shown in Fig. 6 show a mean sizes and relative standard deviations in the same range.
[00088] Example 3 - Soy bean oil and sodium dodecyl sulphate (SDS) in various concentrations.
[00089] The use of sodium dodecyl sulphate (SDS) and influence of the oil concentration was studied in preparations similar to Example 1.
[00090] Soy bean oil (5-15% by weight) from Bio Planete was mixed in 2-propanol and stirred until a clear yellowish solution was obtained. Sodium dodecyl sulphate (SDS) (3% by weight) from Roth was dissolved in water and the printing process described in Example 1 was started using the sodium dodecyl sulphate (SDS) in water solution instead of pure water.
[00091] In every case an opaque and slightly yellowish emulsion was obtained after the preparation. Analysis by dynamic light scattering show a mono-modal size distribution with a mean size of 270 and 288 nm (PDI: 0.24 and 0.25) as shown in Fig. 7 (Size distribu- tion by intensity of soy bean oil (15%) emulsion stabilised by sodium dodecyl sulphate (SDS) after preparation (A) and after 5 weeks (B). Fig. 8 shows a size distribution with a mean size of 213 and 257 nm (PDI: 0.18 and 0.21) (Size distribution by intensity of soy bean oil (5%) emulsion stabilised by sodium dodecyl sulphate (SDS) after preparation (A) and after 5 weeks (B).).
[00092] Example 4 - Soy bean oil and other surfactants.
[00093] The influence of the emulsifϊer was studied in preparations similar to Example 3.
[00094] Soy bean oil (15% by weight) from Bio Planete was mixed in 2-propanol and stirred until the lecithin extract was dissolved and a clear yellowish solution was obtained. A surfactant (sodium dodecyl sulphate (SDS), sodium laureth sulfate (SLES), sodium do- decylbenzene sulfonate (SDBS), egg lecithin (PC), cosmetic emulsifϊer "LV41", disodium- cocoylglutamate, cetyltrimethylammonium bromide (CTAB), sodium cocoamphoacetate, polyethylene glycol sorbitan monooleate (T ween 80), polyethylene glycol octylphenol ether (Triton X-100) and poly ethoxylated fatty alcohol (Dehydol LT7), 3% by weight) is dissolved in water and the printing process as described in Example 3 was started.
[00095] In every case an opaque and slightly yellowish emulsion was obtained after the preparation. Analyses by dynamic light scattering showed a monomodal size distribution with a mean size of 270, 256 and 265 nm (PDI: 0.24, 0.25 and 0.24) as shown in Fig. 9 (Size distribution by intensity of soy bean oil (15%) emulsion stabilised with various surfactants, sodium dodecyl sulfate (SDS) (A), egg lecithine (PC) (B) and cetyltrimethylam- monium bromide (C) (CTAB) (each 3%) - after preparation) and a mean size of 270, 250 and 240 nm (PDI: 0.24, 0.19 and 0.21) as shown in Fig. 10 (Size distribution by intensity of soy bean oil (15%) emulsion stabilised by sodium dodecyl sulfate (SDS) (A), sodium laureth sulfate (SLES) (B) and sodium dodecyl benzene sulfonate (SDBS) (C) (each 3%) after preparation). Analyses of the emulsions stabilised by the other surfactants as de- scribed above [00064] show mean sizes and relative standard deviations in the same range. Analyses after 3-5 weeks showed a mean size of 288, 280 and 251 nm(PDI: 0.25, 0.23 and 0.19) as shown in Fig. 11 (Size distribution by intensity of soy bean oil (15%) emulsion stabilised with various surfactants, sodium dodecyl sulfate (SDS) (A), sodium laureth sulfate (SLES) (B) and sodium dodecyl benzene sulfonate (SDBS) (C) (each 3%) - after 3-5 weeks.).
[00096] Example 5 - Soy bean oil and lecithin at various temperatures.
[00097] The influence of the temperature in respect to emulsion formation was studied in preparations similar to Example 1.
[00098] Soy bean oil (15% by weight) from Bio Planete and egg lecithin (3% by weight) from Sigma (P5394) were mixed in 2-propanol and stirred until the lecithin is dissolved and a clear yellowish solution was obtained.
[00099] During the preparation process, the temperature of the water in the closed loop is set to various temperatures ranging from 6 0C to 45 0C.
[000100] In every case an opaque and slightly yellowish emulsion was obtained after the preparation of the emulsion. Analysis by dynamic light scattering showed a monomodal size distribution with a mean size of 211, 306 and 250 nm (PDI: 0.27, 0.18 and 0.26) as shown in Fig. 12 (Size distribution by intensity of soy bean oil (15%) emulsion at various temperatures, stabilised by lecithin (3%) at 6 0C (A), 15 0C (B) and 35 0C (C) - after preparation and a mean size of 304, 251 and 183/702 nm (PDI: 0.27, 0.26 and 0.39) as shown in Fig. 13 (Size distribution by intensity of soy bean oil (15%) emulsion at various temperatures stabilised by lecithin (3%) at 6 0C (A), 15 0C (B) and 35 0C (C) - 3-5 weeks after preparation. Other preparation temperatures than those as depicted from the experiment above (Fig. 12 and Fig. 13) shown a mean sizes and relative standard deviations in the similar range.
[000101] Example 6 - Various oils and lecithin.
[000102] The influence of the type of oil was studied in preparations similar to those described in Example 1. [000103] An oil (soy bean, castor, coco, linseed, sunflower, walnut, maize seed, sweet almond, jojoba, fish, each 15% by weight) and egg lecithin (3% by weight) from Sigma (P5394) was mixed in 2-propanol and stirred until the lecithin was dissolved and a clear yellowish solution was obtained.
[000104] After the preparation in every case an opaque and slightly yellowish emulsion was obtained. Analysis by dynamic light scattering showed a monomodal size distribution with a mean size of 262, 258 and 270 nm (PDI: 0.25, 0.26 and 0.27) as shown in Fig. 14 (Size distribution by intensity of various oil emulsions, of linseed oil (A), sweet almond oil (B) and fish oil (C) (each 15%) - stabilised by lecithin (3%) after preparation).
[000105] The other oils than those depicted in the results of Fig. 14 shown mean sizes and relative standard deviations in a similar range.
[000106] Example 7 - Fragrances in oil emulsions.
[000107] The printing of fragrant oils was studied in preparations similar to those described in Example 1.
[000108] Soy bean oil (15% by weight) from Bio Planete, a fragrance oil/ingredient (orange, ylang-ylang, carnation, coriander, bergamotte, menthol, each 1% by weight) and egg lecithin (3% by weight) from Sigma (P5394) was mixed in 2-propanol and stirred until the lecithin is dissolved and a clear yellowish solution was obtained.
[000109] After the printing, in every case an opaque and slightly yellowish emulsion with a characteristic scent was obtained. Analysis by dynamic light scattering showed a mono- modal size distribution with a mean size of 300, 256 and 326 nm (PDI: 0.26, 0.24 and 0.24) as shown in Fig. 15 (Size Size distribution by intensity of various oils - (15%) stabi- used by lecithin (3%) and equipped with coriander oil (A), orange oil (B) and menthol (C) (each 1%) after preparation. Preparations with other fragrant oils than those depicted in the results of Fig. 15 shown mean sizes and relative standard deviations in a similar range. [000110] Example 8 - Flavours in oil emulsions.
[000111] The printing of flavoured emulsions was studied in preparations similar to Ex- ample 7.
[000112] Soy bean oil (15% by weight) from Bio Planete, a flavour oil/ingredient (orange, carnation, coriander, bergamotte, menthol, cayenne pepper extract, peppermint, each 1% by weight) and egg lecithin (3% by weight) from Sigma (P5394) was mixed in 2-propanol and stirred until the lecithin is dissolved and a clear yellowish solution was obtained.
[000113] After the printing of the emulsion in every case an opaque and slightly yellowish emulsion with a characteristic scent and taste was obtained. Analysis by dynamic light scattering showed a monomodal size distribution with a mean size of 300, 260 and 277 nm (PDI: 0.26, 0.26 and 0.42) as shown in Fig. 16 (Size distribution by intensity of fragrant emulsions of soy bean oil (15%) stabilised by lecithin (3%) and equipped with coriander oil (A), carnation oil (B) and cayenne pepper extract (C) (each 1%) after preparation. Preparations using the other flavoured oils than those depicted by the results in Fig. 16 shown mean sizes and relative standard deviations in the same range.
[000114] Example 9 - Active ingredients in oil emulsions.
[000115] The ability to print emulsions containing active ingredients was studied in preparations similar to Example 7.
[000116] Soy bean oil (15% by weight) from Bio Planete, an active ingredient (tocopherol (Vitamin E), cod liver oil, clotrimazol (Antifungal medicament), piroxicam (on steroidal anti inflammatory drug), each 1% by weight) and egg lecithin (3% by weight) from Sigma (P5394) were mixed in 2-propanol and stirred until the lecithin was dissolved and a clear yellowish solution was obtained. [000117] After the printing of the emulsion, in every case an opaque and slightly yellowish emulsion was obtained. Analysis by dynamic light scattering showed a monomodal size distribution with a mean size of 218, 307 and 289 nm (PDI: 0.24, 0.24 and 0.24) as shown in Fig. 17 (Size distribution by intensity of emulsions containing various active ingredients with soy bean oil (15%) stabilised by lecithin (3%) equipped with tocopherol (A), clotri- mazol (B) and piroxicam (C) - (each 1%) after preparation). The preparation equipped with cod liver oil showed a mean size of 231 nm and a relative standard deviation (PDI: 0.20) in a similar range.
[000118] Example 10 - Paraffin oil emulsions.
[000119] The influence of the oil concentration was studied in preparations similar to Example 3.
[000120] Paraffin oil (2-15% by weight) from Caelo was mixed in tetrahydrofuran (THF) and a clear solution was obtained. Sodium dodecyl sulphate (SDS) (3% by weight) from Roth is dissolved in water and the printing process described in Example 1 is started using the sodium dodecyl sulphate (SDS) in water solution.
[000121] In every case a colourless (white) emulsion was obtained. Analysis by dynamic light scattering showed a monomodal size distribution with a mean size of 310, 303 and 281 nm (PDI: 0.31, 0.25 and 0.36) as shown in Fig. 18 (Size distribution by intensity of emulsions with concentrations of 15% (A), 5% (B) and 2% (C) of paraffin oil in the cartridge stabilised by sodium dodecyl sulphate (SDS) (3%) after preparation
[000122] Example 11 - Paraffin oil emulsions.
[000123] The influence of the surfactant was studied in preparations similar to Example 10.
[000124] Paraffin oil (15% by weight) from Caelo was mixed in tetrahydrofuran (THF) and a clear solution was obtained. A surfactant (sodium dodecyl sulphate (SDS), sodium dodecyl benzene sulphonate (SDBS), sodium laureth sulphate (SLES) , Plantaren APG 1200, each 3% by weight) was dissolved in water and the printing process described in Example 1 is started using the surfactant in water solution.
[000125] In every case a colourless (white) emulsion was obtained. Analysis by dynamic light scattering showed a monomodal size distribution with a mean size of 334, 356 and 325 nm (PDI: 0.37, 0.28 and 0.36) as shown in Fig. 19 (Size distribution by intensity of paraffin oil (15%) emulsion stabilised by - sodium dodecyl sulphate (SDS) (A), sodium dodecyl benzene sulphonate (SDBS) (B) and sodium laureth sulphate (SLES) (C) (each 3%) after preparation
[000126] Example 12 - Paraffin oil emulsions.
[000127] The influence of the surfactant concentration was studied in preparations similar to Example 10.
[000128] Paraffin oil (5% by weight) from Caelo was mixed in tetrahydrofurane (THF) and a clear solution was obtained. A surfactant (sodium dodecyl sulphate (SDS), sodium dodecyl benzene sulphonate (SDBS), sodium laureth sulphate (SLES)) 3% and 5% by weight was dissolved in water and the printing process described in Example 1 was started using the surfactant in water solution.
[000129] In every case a colourless (white) emulsion was obtained. Analysis by dynamic light scattering showed a monomodal size distribution with a mean size of 303 and 221 nm (PDI: 0.25 and 0.35) as shown in Fig. 20 (Size distribution by intensity of paraffin oil (5%) emulsion stabilised by - sodium dodecyl sulphate (SDS) with concentrations of 3% (A) and 5% (B) after preparation.). Analyses of preparations using sodium dodecyl benzene sulphonate (SDBS) and sodium laureth sulphate (SLES) at concentrations of 3% and 5% showed a mean size and size distributions in a similar range.
[000130] Example 13 - Castor oil - lecithin in various solvents. [000131] The influence of the type of the solvent was studied in preparations similar to Example 1.
[000132] Soy bean oil (15% by weight) and egg lecithin (3% by weight) from Sigma (P5394) are mixed in various solvents (2-propanol, ethanol and tetrahydrofuran (THF) and stirred until the lecithin was dissolved and a clear yellowish solution was obtained.
[000133] After the preparation in every case an opaque and slightly yellowish emulsion was obtained. Analysis by dynamic light scattering showed a monomodal size distribution with a mean size of 204, 198 and 320 nm (PDI: 0.29, 0.23 and 0.28) as shown in Fig. 21 (Size distribution by intensity of oil (15%) emulsion stabilised by lecithin (3%) printed from 2-propanol (A), ethanol (B) and tetrahydrofuran (THF) (C).
[000134] Example 14 - Influence of number of printers.
[000135] The influence of the number of the printers was studied in preparations similar to Example 1.
[000136] Soy bean oil (15% by weight) and egg lecithin (3% by weight) from Sigma (P5394) are mixed in 2-propanol and stirred until the lecithin was dissolved and a clear yellowish solution was obtained.
[000137] During the preparation one or two printers were used.
[000138] After the preparation in every case an opaque and slightly yellowish emulsion was obtained. Analysis by dynamic light scattering showed a monomodal size distribution with a mean size of 256 and 266 nm (PDI: 0.25 and 0.26) as shown in Fig. 22. (Size distribution by intensity of bean oil (15%) emulsion stabilised by lecithin (3%) printed from a single one HP 2000C printer (A) and two HP 2000c printers (B).
[000139] Example 15 - Influence of type of printer cartridge. [000140] The influence of the model of the printer was studied in preparations similar to Example 1.
[000141] Soy bean oil (15% by weight) and egg lecithin (3% by weight) from Sigma (P5394) are mixed in 2-propanol and stirred until the lecithin was dissolved and a clear yellowish solution was obtained.
[000142] During the preparation two different printers (HP 2000C and HP Business InkJet 2200) using different print heads were used.
[000143] After the preparation in every case an opaque and slightly yellowish emulsion was obtained. Analysis by dynamic light scattering show a monomodal size distribution with a mean size of 257 and 218 nm (PDI: 0.25 and 0.25) as shown in Fig. 23 (Size distribution by intensity of soy bean oil (15%) emulsion stabilised by lecithin (3%) printed by HP 2000C printer (A) and HP Business InkJet 2200 printer (B).
[000144] Example 16 - Influence of shape of container.
[000145] The influence of the shape of the container in the first closed loop was studied in preparations similar to Example 1.
[000146] Soy bean oil (15% by weight) and egg lecithin (3% by weight) from Sigma (P5394) are mixed in 2-propanol and stirred until the lecithin was dissolved and a clear yellowish solution was obtained.
[000147] During the preparation of the emulsions containers of various shapes were used in the first closed loop.
[000148] After the preparation in every case an opaque and slightly yellowish emulsion was obtained. Analysis by dynamic light scattering showed a monomodal size distribution with a mean size of 256, 325 and 259 nm (PDI: 0.24, 0.33 and 0.24) as shown in Fig. 24 (Size distribution by intensity of soy bean oil (15%) emulsion stabilised by lecithin (3%) printed into various shapes of container, shape #1 (A), shape #2 (B) and shape #3(C).
[000149] Analyses of preparations using other shapes of container 140 showed a mean size and size distributions in the same range.
[000150] Example 17 - influence of pumping speed.
[000151] The influence of the pumping speed was studied in preparations similar to Ex- ample 1.
[000152] Soy bean oil (15% by weight) and egg lecithin (3% by weight) from Sigma (P5394) are mixed in 2-propanol and stirred until the lecithin was dissolved and a clear yellowish solution was obtained.
[000153] During the preparation the speed of the geared pump 230 in the first closed loop was altered to vary the pumping speed in a linear manner.
[000154] After the preparation in every case an opaque and slightly yellowish emulsion was obtained. Analysis by dynamic light scattering showed a monomodal size distribution with a mean size between of 244, 281 and 284 nm (PDI: 0.24, 0.28 and 0.25) as shown in
Fig. 25 (Size distribution by intensity of soy bean oil (15%) emulsion stabilised by lecithin
(3%) printed into water under pump speed #1, speed #2 and speed #3 of the geared pump
230 of the first closed loop. Increasing pump speed increases the volume exchange rate in container 140. Analyses of preparations using different pump speeds of in the first closed loop shown a mean size and size distributions in a similar range, as shown in Fig. 25 (Size distribution by intensity of soy bean oil (15%) emulsion stabilised by lecithin (3%) printed in water under various pump speeds, speed #1 (A), speed #2 (B) and speed #3 (C) of the pump 230 of the first closed loop).
[000155] Example 18 - influence of point of time of dialysis. [000156] The influence of the point of time of the solvent dialysis was studied in preparations similar to Example 1.
[000157] Soy bean oil (15% by weight) and egg lecithin (3% by weight) from Sigma (P5394) are mixed in 2-propanol and stirred until the lecithin was dissolved and a clear yellowish solution was obtained.
[000158] The dialysis was operated during the preparation of the emulsion and after the completion of the preparation.
[000159] After the preparation and dialysis step in every case an opaque and slightly yellowish emulsion was obtained. Analysis by dynamic light scattering showed a monomodal size distribution with a mean size of 256 and 281 nm (PDI: 0.29 and 0.30) as shown in Fig. 26 (Size distribution by intensity of soy bean oil (15%) emulsion stabilised by lecithin (3%) printed into water under co-solvent removal continuously during preparation (A) and after preparation (B)).
[000160] Example 19 - influence of drop generation principle
[000161] The influence of the drop generation principle was studied in preparations similar to Example 1.
[000162] Soy bean oil (15% by weight) and egg lecithin (3% by weight) from Sigma (P5394) are mixed in 2-propanol and stirred until the lecithin was dissolved and a clear yellowish solution was obtained.
[000163] The preparation was operated using thermal inkjet printers (HP 2000C) and piezo inkjet printers (EPSON StylusColor 300).
[000164] After the preparation and dialysis step in every case an opaque and slightly yellowish emulsion was obtained. Analysis by dynamic light scattering showed a monomodal size distribution with a mean size of 243, 244 and 217 nm (PDI: 0.33, 0.25 and 0.22) as shown in Fig. 27 (Size distribution by intensity of soy bean oil (15%) emulsion stabilised by lecithin (3%) printed into water using thermal inkjet printers (A and B) and a piezo ink- jet printer (C)).
[000165] Example 20 - influence of hydrophobic dye
[000166] The influence of presence of a hydrophobic dye was studied in preparations similar to Example 1.
[000167] Soy bean oil (15% by weight) and egg lecithin (3% by weight) from Sigma (P5394) were mixed in 2-propanol and stirred until the lecithin was dissolved and a clear yellowish solution was obtained.
[000168] The soy bean oil was equipped with a trace of the dye Sudan IV in one case.
[000169] After the preparation and dialysis step in every case an opaque and slightly yellowish or reddish emulsion was obtained. Analysis by dynamic light scattering showed a monomodal size distribution with a mean size of 260 and 277 nm (PDI: 0.34 and 0.27) as shown in Fig. 28 (Size distribution by intensity of soy bean oil (15%) emulsion stabilised by lecithin (3%) printed into water equipped with dye Sudan IV (A) and without dye (B)).
[000170] Example 21 - preparation of a water in oil emulsion
[000171] The possibility of preparation a water in oil emulsion using inkjet devices was studied in a preparation similar to Example 1.
[000172] Water (15% by weight) and polyethylene glycol octylphenol ether (Triton X- 100) (3% by weight) were mixed in 2-propanol and stirred until a clear colourless solution was obtained. [000173] After the preparation an opaque and colourless emulsion was obtained. Analysis by dynamic light scattering showed a monomodal size distribution with a mean size of 1304 nm (PDI: 0.23) as shown in Fig. 29 (Size distribution by intensity of water in oil emulsion stabilised by polyethylene glycol octylphenol ether (Triton X-100) printed into water).
[000174] The above examples illustrate various aspects of the invention for the preparation of emulsions using inkjet technology but do not intend to delimit the invention. The use of different inkjet devices (thermal, piezo, gel (piezo inkjet using a viscous ink), (sole- noid) valve) the use of batch (100) and continuous devices (200); the preparation of oil-in- water and water-in-oil emulsions; the use of different emulsifϊers at different concentrations (egg lecithin, sodium dodecyl sulphate (SDS), sodium laureth sulphate (SLES), sodium dodecyl benzene sulphonate (SDBS), cosmetic emulsifier "LV41", disodiumcocoyl- glutamate, cetyltrimethylammonium bromide (CTAB), sodium cocoamphoacetate, poly- ethylene glycol sorbitan monooleate (T ween 80), polyethylene glycol octylphenol ether (Triton X-100), poly ethoxylated fatty alcohol (Dehydol LT7), Plantaren APG 1200) at 1- 5% by weight; the use of different oils at different concentrations (soy bean, castor, coco, linseed, sweet almond, jojoba, fish, paraffin, sunflower, walnut, maize seed) at 1-15% by weight; the use of different co-solvents at different concentrations and their removal at different points in time (2-propanol, ethanol, tetrahydrofuran (THF)); the emulsification at different temperatures (6 0C - 45 0C); the emulsification of different active ingredients (tocopherol, cod liver oil, clotrimazol, piroxicam); the emulsification of different flavours (orange, carnation, coriander, bergamotte, menthol, cayenne pepper extract, peppermint; the emulsification of different fragrances (orange, ylang-ylang, carnation, coriander, ber- gamotte, menthol); the use of different numbers and models of printers; the use of different shapes of the container, the operation at different pumping speeds of the pump of the first closed loop.
[000175] The invention has been described in terms of illustrative examples. The person skilled in the art will recognise that the invention can be practiced with modification within the scope of the attached claims. At least, it should be noted that the invention is not limited to the detailed description of the invention and/or of the examples of the invention. Reference Numerals
100 Apparatus for batch preparations 105 First immiscible substance
110 Inkj et cartridge
115 Second immiscible substance
120 InkJet printhead
125 Emulsion 130 Droplet jet
135 Emulsifier
140 Container
145 a First heat exchanger
155 S econd heat exchanger 150 Inkj et cartridge opening
200 Apparatus for continuous preparations
210 Tubes
220 Collection reservoir
225 Third heat exchanger 230 (Geared) pump
240 Dialysis cartridge
250 Valves
260 Water reservoir
265 Fourth heat exchanger
270 outlet pipe water reservoir
271 inlet pipe water reservoir
280 outlet pipe collection reservoir
281 inlet pipe collection reservoir 290 Dialysis apparatus

Claims

Claims
1. A method for the manufacture of an emulsion (125) comprising:
- providing (310) a first immiscible substance (105) in at least one inkjet cartridge (110);
- providing (320) a second immiscible substance in a container (140);
- printing (330) the first immiscible substance (105) through an inkjet printhead (120) arranged above the container (140) to emerge as a droplet jet (130) from the inkjet printhead (120) into the container (140) such that the first immiscible substance (105 ) forms the emulsion (125) with the second immiscible substance (115).
2. The method according to claim 1, wherein the inkjet printhead (120) is selected from at least one of a thermal inkjet printhead (120), a piezoelectric printhead (120), or a (solenoid) valve inkjet printhead (120).
3. The method of any one of the above claims, being a batch method for the manufacture of the emulsion (125).
4. The method of any one of claims 1 or 2, being a continuous method for the manufac- ture of the emulsion (125).
5. The method according to any one of the above claims, wherein the first immiscible substance (105) comprises a dispersed phase of the emulsion (125).
6. The method according to the above claims, wherein the second immiscible substance (115) comprises a continuous phase of the emulsion (125).
7. The method according to any one of the above claims, wherein the second immiscible substance (115) is water.
8. The method according any one of the above claims, wherein the second immiscible substance (115) is miscible with a solvent present in the first immiscible substance (105).
9. The method according to any of the above claims, further comprising controlling/selecting the temperature of the first immiscible substance (105) and/or the second immiscible substance (115).
10. The method according to any one of the above claims, further providing an emulsifier (320) (135) in the at least one inkjet cartridge (110) and/or the container (140).
11. The method according to any one of the above claims, further comprising agitating the prepared emulsion (125).
12. The method according to any of the above claims wherein the first immiscible substance is selected from the group consisting of pharmaceuticals, nutraceuticals, foodstuffs, perfumes, flavourants.
13. The method of any one of the above claims, further providing a co-solvent (350) in the inkjet cartridge (110) and/or the container (140).
14. The method according to any one of claims 10 to 13, wherein the emulsifier (135) is selected from at least one of sodium dodecyl sulphate (SDS), egg lecithin (PC), cetyl- trimethylammonium bromide (CTAB), sodium laureth sulfate (SLES), sodium dodecyl benzene sulfonate (SDBS), egg lecithin from Sigma (P5394), sodium dodecylbenzene sulfonate (SDBS), cosmetic emulsifier "LV41", disodiumcocoylglutamate, cetyl- trimethylammonium bromide (CTAB), sodium cocoamphoacetate, polyethylene glycol sorbitan monooleate (T ween 80), polyethylene glycol octylphenol ether (Triton X- 100), poly ethoxylated fatty alcohol (Dehydol LT7) and Plantaren APG 1200.
15. The method of any one of claims 10 to 14, further comprising removal (360) of the co- solvent.
16. The method of any one of claims 10 to 15, wherein following an at least partial removal of the co-solvent, a portion of the co-solvent remains in the manufactured emulsion (125).
17. The method of any one of the above claims, further selecting a temperature during dialysis removal of co-solvent.
18. The method according to any one of the above claims, wherein either the first immis- cible substance (105) or the second immiscible substance (115) is an aqueous miscible substance.
19. An apparatus (100) for the manufacture of an emulsion (125) comprising: at least one inkjet cartridge (110) containing at least a first immiscible substance (105) and having at least one inkjet printhead (120); and an inkjet cartridge opening (150) adapted to supply the first immiscible substance
(105) and/or an emulsifϊer (135), a container (140) positioned underneath the inkjet printhead (120) and containing a second immiscible substance (115), such that the first immiscible substance (105) is printed through the inkjet printhead
(120) to form the emulsion (125) in the container (140).
20. The apparatus (100) according to claim 19, wherein the inkjet cartridge (110) is a thermal inkjet cartridge (110), a piezoelectric inkjet cartridge (110), or a (solenoid) valve inkjet cartridge (110).
21. The apparatus (100) of any one of claims 19 to 20, wherein the first immiscible substance (105) is a bio-active substance.
22. The apparatus (100) according to any of claims 19 to 21 further comprising: an agitator for agitating the second immiscible substance (115) and/or emulsion (125) to aid the formation of the emulsion (125).
23. The apparatus (100) according to any of claims 19 to 22 further comprising: a first heat exchanger (145 a) for heating or cooling the first immiscible substance (105) and/or an emulsifϊer (135); and/or a second heat exchanger (155) for heating or cooling the second immiscible substance (115) and/or the emulsion (125).
24. An apparatus (200) for the continuous manufacture of emulsions comprising: an apparatus (100) for the manufacture of an emulsion (125) according to anyone of claims 19 to 23, a dialysis apparatus (290) a plurality of (geared) pumps (230) a plurality of valves (250) a collection reservoir (220) a plurality of inlet and outlet pipes (270, 271, 280, 281, 150).
25. The apparatus (200) according to claim 24, wherein the dialysis apparatus (290) comprises a fourth heat exchanger (265) for heating or cooling water in a water reservoir (260).
26. The apparatus (200) according to any one of claims 24 or 25, wherein the collection reservoir (220), comprises a third heat exchanger (225) for heating or cooling the manufactured emulsion (125).
27. The apparatus (200) according to any one of claims 19 to 26, wherein the container (140) is a continuous- flow reservoir wherein, in use, the first immiscible substance (105) and second immiscible substance (115) is replenishable as the manufactured emulsion (125) is removed from the collection reservoir (220).
28. The apparatus (200) according to any one of claims 19 to 27, wherein the dialysis apparatus (290) is used to remove a water miscible co-solvent.
29. A use of the apparatus according to any one of claims 19 to 28 in a continuous- flow process for the manufacture of an emulsion (125).
PCT/EP2008/066476 2007-11-30 2008-11-28 Inkjet printer for the manufacture of emulsions WO2009068673A1 (en)

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