Abstract:
Process for producing a core shell particle comprising the steps of: a. Introducing inorganic particles into an aqueous phase b. Adding a hydrophobic substance and making an emulsion of the hydrophobic substance in the aqueous phase c. Adding inorganic particles precursors to the emulsion until an inorganic shell made from inorganic particles precursors and inorganic particles of step a. is created around hydrophobic droplets.

Description:
TECHNICAL FIELD OF THE INVENTION 
       [0001]    The present invention relates to a core shell particle and to a method for manufacturing the same. 
       BACKGROUND OF THE INVENTION 
       [0002]    WO2004/024209 describes materials and methods for use in delivering substances. It particularly discloses core-shell particle having a core encapsulated within a calcium carbonate shell, with an intermediate layer composed of an amphiphilic compound surrounding the core. The core-shell particles are produced by a method comprising forming an emulsion droplet, contacting the emulsion droplet with a calcium solution, adding Mg to the solution and adding a short chained acid polymer to the solution. Uses of the core shell particles are described wherein substances in can be absorbed into the core shell particles. Other uses are described where the core shell particles are used to deliver pharmacological agents. 
         [0003]    One major disadvantage of this manufacturing process is the required use of an amphiphilic compound and a polymer which are moreover retained in the final product. 
         [0004]    Stabilising an emulsion by using powders (e.g. colloidal silica) which adsorb at the interface has been known since Pickering, nonetheless, this does not result in core-shell particles which can be removed from the continuous aqueous phase. 
         [0005]    There is therefore a need for core-shell particles which can be produced without using amphiphilic compounds and which moreover do not contain said amphiphilic compounds. 
         [0006]    Tests and Definitions 
         [0007]    Particle Diameter 
         [0008]    Core shell particle diameter was measured by microscopy. 
         [0009]    Long Chain 
         [0010]    Long chain means 16 carbon atoms or more. 
         [0011]    Lipids 
         [0012]    Lipids mean long chain fatty acids or long chain alcohols 
         [0013]    Oils or Fats 
         [0014]    Oils and fats mean compounds containing more than 80% triglycerides. They can also contain diglycerides, monoglycerides and free fatty acids. 
         [0015]    Hydrocarbon Oils 
         [0016]    Hydrocarbon oils mean alkane containing at least 6 carbon atoms 
         [0017]    Hydrophobic Compounds 
         [0018]    Hydrophobic compounds means lipids, oils or fats, hydrocarbon oils, silicon oils or any mixture thereof, either pure or containing compounds in solution. Hydrophobic compounds can also contain particles in suspension. 
       GENERAL DESCRIPTION OF THE INVENTION 
       [0019]    It is a first object of the present invention to provide core-shell particles characterised in that they consist in a hydrophobic core and an inorganic shell. 
         [0020]    Preferably, the inorganic shell is made of carbonate, phosphate, sulphate, silicate, metal oxides, clay or any mixture thereof. More preferably the inorganic shell is made out of carbonate, phosphate or any mixture thereof. Even more preferably the inorganic shell is made out of calcium carbonate. 
         [0021]    The hydrophobic core contains one or more hydrophobic compounds. Hydrophobic compounds used in the present invention are preferably oils or fats. Preferably, the hydrophobic core contains at least 50% w/w hydrophobic compounds, more preferably at least 75% w/w, even more preferably at least 95% w/w. 
         [0022]    The core-shell particles of the invention preferably have a diameter of between 0.2 and 500 microns, preferably above 1 micron, more preferably above 10 microns. Preferably also the particles have a diameter of less than 50 microns. 
         [0023]    Preferably, the inorganic shell is not porous. It means that after having been washed with solvent in order to remove residual hydrophobic material on the outside of the inorganic shell, hydrophobic compounds remain inside the inorganic shell. 
         [0024]    It is a second object of the present invention to provide a process for producing a core shell particle according to any preceding claim and comprising the steps of:
       a. Introducing insoluble inorganic particles into an aqueous phase   b. Adding a hydrophobic compound and making an emulsion of the hydrophobic compound in the aqueous phase   c. Adding inorganic particles precursors to the emulsion until an inorganic shell made from inorganic particles precursors and inorganic particles of step a. is created around hydrophobic droplets.       
 
         [0028]    The addition of the precursors leads to the precipitation of further inorganic material which can be identical to, or different from, the material constituting the inorganic particles of step a. The inorganic particles of step (a.) act as nucleation points for the formation of a solid shell around the droplets. 
         [0029]    In order to avoid a bulk precipitation of the inorganic particles precursors, the rate of addition of said inorganic particles precursors must be sufficiently slow, otherwise the precursor, instead of precipitating around the existing inorganic particles will precipitate in the solution (bulk precipitation). 
         [0030]    Inorganic particles precursors of step c. are combinations of cations and anions which form a precipitate. Inorganic particles precursors of step c. comprise
       cations of group II metals as well as transition metal ions or any mixture thereof and,   anions of the group consisting of carbonates, phosphates, chlorides sulfonates or sulphates ions, or any mixture thereof.       
 
         [0033]    The inorganic material which precipitates in step c. can be identical to, or different from, the material which constitutes the inorganic particles of step a. 
         [0034]    During the formation of the inorganic particles in step c, pH drops, it is thus advantageous to add a pH adjuster such a NaOH at this step to avoid having the pH dropping below the precipitation pH of the inorganic particles precursors. Otherwise, precipitation would stop prematurely. 
         [0035]    In a preferred embodiment of the invention core shell particles are then separated from the aqueous phase. 
         [0036]    The cores shell particles can then be washed with a solvent to remove hydrophobic compounds which can still present on the outside surface, the core shell particles are then dried to form a free flow powder. 
     
    
     DETAILED DESCRIPTION OF THE INVENTION 
       [0037]    The invention will be further described in the following examples. 
       EXAMPLE 1 
     For Making a Shell with CaCO3 Crystal 
       [0000]    
       
         
           
             1. 8 g precipitated CaCO3 particle (Marco calcium, Japan) is dispersed in 200 g de-ionised water at a pH value of 8.5, using ammonium chloride and ammonium hydroxide to control the pH. A Silverson is used to disperse the particle at 4000 rpm for 5 mins. 20 ml (18 g) food grade sun flower oil is then added slowly to the dispersion at 4000 rpm Silverson speed. After 2 mins a stable emulsion is formed. 
             2. The emulsion is then transferred to a one liter reaction vessel. A over head stirred is used to agitate the emulsion at 150 rpm. CO2 is then introduced to the vessel at a 0.02 partial pressure during the whole process. CaCl2 solution is introduced using a pump. During the process NaOH solution is also introduced into the vessel to control the emulsion pH constant at 8.5. In order to control the growth rate and thickness of the CaCO3 shell the concentration and flow rate of the CaCl2 solution is controlled. Typically the flow rate and concentration of CaCl2 solution are kept low at the beginning of the process. High flow and concentration are used in later stage. Concentrations and flow rates of CaCl2 solutions used in the process as a function of time were as follows:
           For 2 hours, 16.5 ml per hour of 0.07 mol/l of CaCl2 solution   For further two hours, 16.5 ml per hour of 0.7 mol/l of CaCl2 solution   For further two hours, 16.5 ml per hour of 3.5 mol/l of CaCl2 solution   For further two hours, 28 ml per hour of 4.0 mol/l of CaCl2 solution   
         
             3.After the reaction the particles are separated from the liquid filtration. The particles are washed with de-ionised water and then put in 200 ml ethyl acetate with gentle agitation for 2 minutes. It is then separated from the solvent and dried in a vacuum oven at room temperature for 24 hours. Free flow powder is obtained. 
           
         
       
     
       EXAMPLE 2 
       [0045]    Commercial perfumes currently used in UK Comfort Blue fabric conditioner were used to replace sun flower oil in Example 1. 
       EXAMPLE 3 
       [0046]    Mixtures of limonene and sun flower oil, from 50% to 10% of limonene used as the hydrophobic phase. 
       EXAMPLE 4 
       [0047]    Mixture Basil 20% in sun flower oil is as the hydrophobic phase. 
       EXAMPLE 5 
       [0048]    Mixture of cocktail flavor and sun flower oil (1:9 volume) is as the hydrophobic phase. Cocktail flavor contains Trans-2-hexenal, cis-3-hexenol, cis-3-hexenyl acetate, carvone, ethyl octanoate and L-limonene(the same volume in the cocktail flavor). 
       EXAMPLE 6 
       [0000]    
       
         
           
             1. 1.2 g CaCO3 particle (Marco calcium, Japan) is dispersed in 30 ml deionised water at a pH value of 8.5, using ammonium chloride and ammonium hydroxide to control the pH. A Silverson is used to disperse the particles at 4000 rpm for 5 mins. 3 ml food grade sun flower oil is then added slowly to the dispersion at 4000 rpm Silverson speed in 5 mins 
             2. 25 ml 0.1M CaCl2 and 25 ml 0.1M NaHCO3 solutions are added into the emulsion separately at 12.5 ml/h for the first 2 hours 
             3. 25 ml 0.2M CaCl2 and 25 ml 0.2M NaHCO3 solutions are added into the emulsion separately at 12.5 ml/h for the following 2 hours 
             4. 25 ml 0.5M CaCl2 and 25 ml 0.5M NaHCO3 solutions are added into the emulsion separately at 12.5 ml/h for the following 2 hours 
             5. 25 ml 1.0M CaCl2 and 25 ml 1.0M NaHCO3 solutions are added into the emulsion separately at 12.5 ml/h for the following 2 hours 
             6. Capsules separated by filtration 
             7. Deionised water and Ethyl acetate washing and then drying in vacuum. 
           
         
       
     
       EXAMPLE 7 
     For Making a Shell with CaCO3 and Dicalcium Phosphate Dihydrate Crystals 
       [0000]    
       
         
           
             1. 0.8 g CaCO3 particle (Marco calcium, Japan) is dispersed in 20 ml deionised water. A Silverson is used to disperse the particles at 4000 rpm for 5 mins. 2.0 ml food grade sun flower oil is then added slowly to the dispersion at 4000 rpm Silverson speed in 5 mins. 
             2. 5 ml 0.015M CaCl2 and 5 ml 0.01M K 2 HPO 4 /KH 2 PO 4  (1:1 molar ratio) solutions are added into the emulsion separately drop by drop for the first 2 hours. 
             3. 5 ml 0.15 M CaCl2 and 5 ml 0.1M K 2 HPO 4 /KH 2 PO 4  (1:1 molar ratio) solution are added into the emulsion separately drop by drop for the following 2 hours. 
             4. 5 ml 1.5M CaCl2 and 5 ml 1M K 2 HPO 4 /KH 2 PO 4  (1:1 molar ratio) solution are added into the emulsion separately drop by drop for the following 2 hours. 
             5. Capsules separated by filtration 
             6. Deionised water and Ethyl acetate washing and then drying in vacuum.