GB2623111A

GB2623111A - New methods for production of hollow particles

Info

Publication number: GB2623111A
Application number: GB2214715.1A
Authority: GB
Inventors: Filtvedt Werner; Filtvedt Josef; Hiort Marianne; Marie Johnsen Hennie; Klaveness Jo; Storli Robert
Original assignee: Nacamed AS
Current assignee: Nacamed AS
Priority date: 2022-10-06
Filing date: 2022-10-06
Publication date: 2024-04-10
Also published as: GB202214715D0

Abstract

A process for the production of hollow particles from coated elemental silicon particles, wherein the elemental silicon particles are reacted with water. The hollow particles may be oxidized silicon (silicon dioxide, SiO2), and the process may comprise oxidising the elemental silicon particles at the surface by oxygen or air, suspending and stirring the oxidised particles in water of pH 7 or above until hydrogen (H2) is no longer released, and either using the hollow particles directly or isolating and drying them. The hollow particles may be hollow coated silicon particles formed via the oxidation of the surface of the elemental silicon particles, followed by coating the oxidised particles with an inorganic or organic material before being reacted with water at a pH of 7 or above. The hollow coated particles may be free from silicon and formed from coated silicon particles, wherein the coating may be an inorganic or organic material. The hollow particles may be dried using low pressure plus heat, spray drying or freeze drying. The silicon particles can be prepared from a non-CVD process e.g. grinding and/or milling or from a CVD method.

Description

New methods for production of hollow particles

Field of the invention

The present invention relates to new methods for production of hollow particles, especially silicon hollow particles. More specifically, the production processes are characterized by forming an insoluble shell around elemental silicon particles followed by a chemical reaction wherein the silicon particles dissolve.

Background

Hollow particles are particles comprising a shell with no solid material inside the shell. Such particles, including hollow silicon particles might have applications within thermal insulation, drug delivery, lithium batteries and as catalysts for various chemical and biological processes. (i. Hussain et al. Hollow nano-and microstructures: Mechanism, composition, applications, and factors Affecting morphology and performance in Coordination Chemistry Reviews 458 82022 214429, ('.Takai-Yamashita et al. Hollow silica nanoparticles: A tiny pore with big dreams in Advanced Powder Technology 31(2020) 804-807, J. Sharma et al. Hollow Silica Particles: Recent Progrcss and Future Perspectives in Nanomateria1s 10,2022,1599.).

The processes for preparation of hollow silica include coating of micelles/emulsions with silica (Sith) followed by calcination and dissolution of the micelle/emulsion material, and a Stoeber process forming a silica coating around polymer particles or bacteria/virus followed by calcination at high temperature. In the Stoeber process organic silicon compounds are used to prepare silica (SiO2) particles. Other methods include coating of inorganic particles with silica using the Stoeber process followed by calcination and dissolution, and polymer adsorption on silica particles followed by etching. The solid silica particle etching process is described in H. Zhang et al. Synthesis of hollow ellipsoidal silica nanostnictures using a wet-chemical etching process in J. Colloid and interface Science 375(2012)106-111 and W. Li et al investigation of selective etching mechanism and its dependency on the particle size in preparation of hollow silica spheres in J. Nanopart. Res. 17(2015)480. (From Nanomaterials 10,2022,1599). Both H. Zhang and AV. Li use silica particles.

The present process is not based on silica particles (SiO2) but silicon particles where the silicon is just elemental silicon. In elemental silicon the silicon has oxidation level zero while in silica the silicon has oxidation level plus four.

Summary of the invention

In a first aspect, the invention provides a new method for production of hollow particles from coated silicon particles comprising elemental silicon.

In one aspect of the present invention the coating is oxidized silicon.

In another aspect of the present invention, the coating is in the form of silicon plus a non-silicon material.

In a third aspect ofthe present invention, the coating is only a non-silicon material.

In all aspects of the present invention, water at pH 7 or above is preferably used to dissolve the elemental silicon.

Definitions The term "porous-particles refer to particles with pores and not a smooth surface. Porous particles can be prepared by an etching process typically using hydrofluoric acid or by a process where smaller particles fonn aggregates with pores.

The tenn "mesoporous-particles refer to particles containing pores with diameters between 2 and 50 nm.

The term "microporous" particles refer to particles having pores smaller than 2 nm in diameter.

The term "macroporous" particles refer to particles having pores larger than 2 nm in diameter.

The term " CVD" silicon particles refer to a process where the particles have been prepared by a chemical vapor deposition preferably using silane gas.

The tenn non-CVD" silicon particles refer to a process where the particles have not been prepared directly by a chemical vapor deposition Such particles are typically prepared by grinding of larger silicon materials.

The term cCVD-SP is used to denote "centrifuge Chemical Vapor Deposition Silicon Particles' and refers to silicon particles which have been prepared by a centrifuge method. In particular, this term refers to silicon particles which have been prepared by a CVD method in a reactor wherein the reactor comprise a reactor body and a rotation device operatively arranged to the reactor, wherein the rotation device is configured to rotate the reactor around an axis during production of said silicon comprising particles.

The tenn PcCVD-SP is used to denote "Porous centrifuge Chemical Vapor Deposition Silicon Particles" and refers to silicon particles which have been prepared by a centrifuge method, optionally followed by a process to prepare the porosity of the particles.

Detailed Description

The present invention relates to new methods for the production of hollow particles from particles comprising elemental silicon and a coating. The elemental silicon reacts with water (pH at 7 or above) and dissolves while the coating is not soluble in the aqueous solution.

In one embodiment, the invention provides a new method for the production of hollow particles from coated silicon particles comprising elemental silicon where the coating is oxidized silicon.

The process is preferably characterized by the following steps: 1. Elemental silicon particles are oxidized at the surface. One preferred method for this oxidation is to keep the silicon particles in presence of an oxidating agent like for example air or oxygen at ambient temperature for given time. The oxidation might also be performed by use of other oxidative agents.

2 The particles are suspended and stirred in water with pH 7 or above until no more hydrogen gas is released from the suspension.

3. The formed hollow particles are used directly or preferably isolated and dried.

The typical product from this process will be hollow silicon particles made out of a silicon oxide.

The conditions in step 1 determine the thickness of the shell in the final hollow particles. Increase in temperature and reaction time will increase the amount of oxidation and thereby increase the thickness of the shell.

One prefened aspect of the present invention relates to methods for the preparation of hollow particles where the thickness of the shell can be predetermined by the level of oxidation in the first step. Minor oxidation of the elemental silicon in the first step will generate hollow particles with thin shells, while extensive oxidation will increase the shell thickness.

Pure oxygen will be more active in the oxidation process than oxygen gas mixtures like air.

Other oxidative processes for elemental silicon are described in the chemical literature and include among others hydrogen peroxide Advantages with the present process include the simplicity of the process and the lack of expensive and toxic chemicals. Elemental silicon particles are easily available as discussed below and the other chemicals are safe and do not represent an environmental problem. The process with water, air and optionally some basic substance can be regarded as a green chemical process.

In a second embodiment of the present invention, the coating is in the form of silicon plus a non-silicon material.

The process is preferably characterized by the following steps:

S

1 Elemental silicon particles are oxidized at the surface. One preferred method for this oxidation is to keep the silicon particles in presence of an oxidating agent like air or oxygen or another oxidative agent at ambient temperature for given time.

2. The particles are coated with an inorganic or organic material using well-known methods.

3. The particles are suspended and stirred in water with pH 7 or above until no more hydrogen gas is released from the suspension.

4. The formed hollow particles are used directly or preferably isolated and dried.

The typical product from this process will be hollow silicon particles made out of a silicon oxide coated with carbon, organic materials or inorganic materials.

Compared to other processes for preparation of similar products, the present process might have the same advantages as discussed above In a third embodiment of the present invention, the coating is only a non-silicon material. The process is preferably characterized by the following steps: 1. The particles are coated with an inorganic or organic material using well-known methods.

2. The particles are suspended and stirred in water with pH 7 or above until no more hydrogen gas is released from the suspension.

The typical product from this process will be hollow silicon-free particles made out of a carbon, organic materials, for example polymers and inorganic materials.

Compared to other processes for preparation of similar products, the present process might have the same advantages as discussed above.

In all these embodiments additional steps could optionally be included: A step on use of surfactants to secure good dispersion of the particles in the aqueous phase during the reaction.

A step on washing the hollow particles using water and/or organic solvents or a mixture thereof.

A step on isolation of the hollow particles typically by a centrifugation step or a filtration step.

A step on drying particles using low pressure plus heat spray drying or freeze drying.

Further preferred aspects of the present invention might relate to the pH in the aqueous phase during reaction of silicon with water forming hydrogen. Preferred pH is above 7, more preferred above 7.5, even more preferred above S. Further preferred aspects of the present invention might relate to the temperature in the aqueous phase during reaction of silicon with water forming hydrogen. Preferred temperature is ambient temperature or above, more preferred temperature is 30 degrees centigrade or above.

Silicon particles used in the process The silicon particles comprise mainly elemental silicon.

In another preferred embodiment of the invention, the hollow particles are prepared according to the present process using elemental silicon particles prepared from a non-CVD process. Such particles can typically be produced from a grinding and/or milling processes.

In another preferred embodiment of the invention, the elemental silicon particles used in the above processes are prepared by a CVD method which does not comprises a grinding and/or milling step.

In a particularly preferred embodiment of the present invention, elemental the silicon particles used in the present invention are centrifuge Chemical Vapor Deposition Silicon Particles (cCVD-SP). A particularly preferred method for the preparation of the silicon particles is disclosed in WO 2013/048258 and is briefly described below.

In one particularly preferred embodiment of the present invention, the silicon particles used in the present invention are non-porous centrifuge Chemical Vapor Deposition Silicon Particles (cCVD-SP).

In one particularly preferred embodiment of the present invention, the silicon particles used in the present invention are porous centrifuge Chemical Vapor Deposition Silicon Particles (PcCVD-SP). A particularly preferred method for the preparation of the silicon particles is disclosed in WO 2013/048258 and is briefly described below.

In this preferred process, chemical vapor deposition is carried out in a reactor comprising a reactor body that can rotate around an axis with the help of a rotation device operatively arranged to the reactor, at least one sidewall that surrounds the reactor body, at least one inlet for reaction gas, at least one outlet for residual gas and at least one heat appliance operatively arranged to the reactor, characterized in that during operation for the manufacture of silicon particles by CVD, the reactor comprises a layer of particles on the inside of, at least, one side wall.

Thus, the CVD process is preferably characterized by: - producing a particle layer from the silicon containing reaction gas in the reactor or importing particles for the formation of an inner particle laver on the inner wall surface of the reactor, - importing reaction gas for chemical vapor deposition, - producing silicon by chemical vapor deposition on the particle layer, -loosening the produced silicon from the particle layer and taking it out and carrying out any preparation of the inner surface of the reactor before the production of the silicon is continued by repeating the steps of the method.

Depending on the application the particles may be coated inert or exposed to air to form a thin native oxide layer on the particles. Further processing may include etching of the particles in HF with or without subsequent coating depending on the application However, preferably, the particles are not subject to an etching process.

In a particle formed from milling of electronic grade silicon wafers the average crystal size of the material will be many orders of magnitude larger than the particle size. For CVD formed particles the average crystal size is tunable. it is possible to have one or few ciystallites within each particle, to have a number of nano-crystallites within each particle or to have a completely un-ordered amorphous structure. This is tunable by the process and it is therefore both possible to choose a particular crystallinity or average crystallite size for the specific application or according to further processing. For instance will the etching speed depend on the crystallite size and orientation as well as the defect distribution and frequency within each crystal.

The particle degradation time will to some degree depend on the number of crystal interfaces reaching the surface in other words how many oxidation channels the oxidation may propagate along down into the material as well as how imperfect the individual crystals are. The more imperfections and interfaces the easier it is both to reach the individual silicon atoms and to oxidize them. Since these are tunable properties in a CVD produced material it is thus possible to tune the material to any specific application in a completely different way than for a crushed large crystals material where these properties are given. Especially for applications where rapid bio-degradation is desirable the CVD particles will have a substantial advantage over the classical crushed crystalline silicon.

In a further preferred aspect of the present invention, the silicon particles used in the above processes are porous particles.

In a further preferred aspect of the present invention, the silicon particles used in the above processes are non-porous particles.

As discussed previously, the silicon particles of the invention are capable of generating hydrogen.

The silicon particles have the capability of reacting with water but has been found to be much less reactive towards deuterium oxide, however, if the pH is sufficient high especially in combination with higher temperature, the silicon particles react with deuterium oxide and form deuterium gas.

The silicon in the silicon particles used in the present process (typically cCVD-SP) is present in at least 50 wt % as elemental silicon (silicon with oxidation number 0), relative to the total weight of silicon. More preferred form of silicon in the present silicon particles is at least 70 wt % as elemental silicon, even more preferred at least 80 wt% as elemental silicon, relative to the total weight of silicon. Another preferred aspect related to the form of silicon in the present particles is that the amount of elemental silicon and silicon dioxide is more than 80%, more preferably more than 90% most preferably more than 95%, relative to the total weight of silicon.

The elemental silicon in the particles used in the present process may be in amorphous or crystalline form. The elemental silicon in particles produced by the CVD process is mainly in the form of amorphous elemental silicon at ambient temperature, however, particles comprising crystalline silicon can directly be prepared by CVD at high temperature (e.g, 600 °C and above) and longer reaction times. The particles comprising crystalline silicon prepared from a CVD method typically are in the form ofpolycrystalline material (clystal size around 1.5 nm) while crystalline milled particles typically consist of one crystal of silicon.

The crystalline versus amorphous form of silicon can routinely be determined by X-ray diffraction analysis (XRD analysis). The amorphous form of silicon can be transformed to crystalline form of silicon by heating to relative high temperatures (e.g. above 500 °C).

Silicon particles produced by the CVD method typically comprise some material comprising one or more silicon-hydrogen bond. This hydrogen might be available for formation of some hydrogen gas in a reaction with water.

In certain embodiments, the elemental silicon is present in a crystalline form, in some embodiments typically more than 50 wt% in the crystalline form and in some embodiments more than 70 wt% in a crystalline form and finally in some embodiments more than 90 wt% in a crystalline form, relative to the total weight of elemental silicon.

In other embodiments, the silicon particles comprise elemental silicon in amorphous form, in some embodiments more than 50 wt%, in some embodiments more than 70 wt%, in some embodiments more than 90 wt% and finally in some embodiments more than 95 wt% in amorphous form, relative to the total weight of elemental silicon.

One preferred embodiment of this aspect of the invention is wherein the silicon particles are cCVD-SP or PcCVD-SP.

One of the most preferred embodiments of this aspect of the invention is wherein the silicon particles are cCVD-SP comprising silicon in amorphous form, such as in the wt% ranges defined above.

Another of the most preferred embodiments of this aspect of the invention is wherein the silicon particles are cCVD-SP that are not produced by an etching process; especially not by an hydrofluoronic (HF) etching process, i.e. the silicon particles are non-etched.

The ultimate form of the most preferred embodiments of this aspect of the invention is wherein the silicon particles comprise amorphous silicon, such as in the wt% ranges defined above, and are non-etched.

Particle size The silicon particles may have "tailor made" particle size. Typical median diameter for the silicon particles of the invention may be less than 500 nm, such as 30 to 300 nm, using the technique of Dynamic Light Scattering (DLS), for example using instruments like Zetasizer. The given particle sizes are related to the final silicon particles loaded with one or more drug substances and optionally excipients and coating.

The polydispersity index can also vary from almost rnonodisperse particles to particles with very broad particle size distribution.

In one embodiment, the silicon particles preferably have an average diameter of less than pm, more preferably less than 0.8 tun, even more preferably less than 0.6 tun, such as less than 0.5 pm Porosity The silicon particles of the invention can be non-porous (cCVD-SP) or porous (PcCVDSP). In all embodiments, it is preferred if the particles are prepared by a non-etching process. Porous particles can be prepared by fonning stable aggregates of smaller particles; so-called stable particle clusters.

The porosity of the PcCVD-SP can vary over a large range depending upon choice of application. The porosity is a measure on the volume of the pores. A PcCVD-SP with porosity of 50 % has a porosity volume that is 50% of the total PeCVD-SP volume. The porosity of PcCVDSP may typically be from 20% to 90%. In certain embodiments, the porosity is more than 40%, typically more than 50%, more than 60%, more than 70%, more th'm 80% such as 90%. In other embodiments the porosity is preferably around 50% or lower.

In one embodiment, the particles are microporous. In this embodiment, preferably at least 2 vol% of the pores are micropores, more preferably at least 5 vol%, even more preferably at least 10 vol%, especially at least 20 vol%, such as at least 50vol%, relative to the total pore volume.

In another embodiment, the particles are mesoporous. In this embodiment, preferably at least 2 vol% of the pores arc mcsoporcs, more preferably at least 5 vol%, even more preferably at least 10 vol%, especially at least 20 vol% such as at least 50vol%, relative to the total pore volume.

In a further embodiment, the particles arc macroporous. In this embodiment, preferably at least 2 vol(l'^) of the pores are macropores, more preferably at least 5 vol%, even more preferably at least 10 vol%, especially at least 20 vol%, such as at least 50vol% relative to the total pore volume Particle surface and coating The particle surface can typically be in the form of elemental silicon or more preferably in the form of a layer of silicon oxide where the elemental silicon on the particle surface has undergone a natural or a chemical oxidation process. The surface might also be covered by a layer of drug molecules that are covalently or non-covalently bound to the silicon-comprising material. The surface might also be covered by a coating material comprising carbon, preferably in the form of an organic coating. The organic coating might be bonded to the silicon comprising material by covalent or non-covalent bonds. The chemistry of coating of silicon particles is well known in the art.

An optional coating might have one or more different functions in addition to forming the shell in the present hollow microparticle shell depending on the function of the material. This includes: * The coating might improve the physical stability of the hollow particles.

* The coating might improve the chemical stability of the hollow particles.

* The coating might control the release profile of a drug substance.

* The coating might improve the insulation properties.

* The coating might improve the properties for use in batteries.

The coating might from a chemical perspective have one or more of the following properties: * Hydrophilic coating for example in the form of eovalently attached polyethylene glycol chains.

* Positively charges particle surface at physiological pH. This can typically be obtained by attachment of aliphatic amino groups to the particle surface.

* Negatively charges particle surface at physiological pH. This can typically be obtained by attachment of carboxylic groups to the particle surface.

* Enzymatically degradable coating Typical coatings include for example coatings comprising ester groups.

* Coatings comprising a monolayer of coating molecules.

* Coatings comprising multilayer of coating molecules.

* Coating comprising elemental carbon.

* Coatings based on monomer compounds * Coatings based on polymer compounds * Coatings based on phospholipids and/or other lipid derivatives.

* Coatings based on proteins, peptides or amino acids or derivatives thereof * Coatings based on sugar molecules; including, monosaccharides, disaccharides, oligosaccharides including cyclodextrins and polysaccharides.

The surface area of the silicon particles of the invention will vary. The surface area will typically be much higher for porous particles (PcCVD-SP) than non-porous particles (cCVDSP). The surface area of the particles prior to loading of the at least one drug substance may be up to 1000 m2 per gram particles.

Preferred coatings include surfactants like for example ceteareth, cetearyl, ceteth, cocamide, isosteareth, laureth, lecithin, olcth PEG-20 almond glycerides, PEG-20 methyl glucose sesquistearate, PEG-25 hydrogenated castor oil, PEG-40 sorbitan peroleate, PEG-60 Almond Glycerides, PEG-7 olivate, PEG-7 Glyeeryl cocoate, PEG-8 dioleate, PEG-8 laurate, PEG-8 oleate, PEG-80 sorbitan laurate, Polysorbates and Pluronics

Description of Figures

Figure 1: TEM images of the sample from Example 1 withdrawn after 50 min. Figure 2: TEM images of the sample from Example I withdrawn after 200 min Figure 3: TEM images ofthe sample from Example 2.

The invention will now be described with reference to the following, non-limiting, examples.

Examples

All CVD silicon particles were produced in a reactor wherein the reactor comprise a reactor body and a rotation device operatively arranged to the reactor, wherein the rotation device is configured to rotate the reactor around an axis during production according to W02013048258.

Example 1: Preparation of hollow silica spheres after 1) air oxidation to form Si02 shell, and 2) dissolution of Si core at pH 7.4 Silicon particles (amorphous silicon, hydrodynamic diameter 210 nm with polydispersity index of 0.180) were exposed to ambient air at room temperature for 10 min and stored at ambient atmosphere for up to one month to form a passive oxide layer. The particles (50 mg) were then suspended in 25 ml phosphate-buffered saline (PBS) of pH 7.4. The suspension was stirred at 37 degrees centigrade.

One sample of 4.5 ml was taken out after 50 min immersion and centrifuged (10 min, 14k rpm) to separate particles from the solution. Another sample of 4.5 ml was taken out after 200 min immersion and centrifuged to separate particles from the solution. The supernatants were removed and the pellets were resuspended and stored in ethanol until transmission electron microscopy (TEM) imaging.

The samples were diluted in isopropanol before a droplet was transferred to a copper TEM grid. TEM imaging was performed with a double spherical aberration corrected coldFEG JEOL ARM 200FC, operated at 200 kV. Simultaneous Energy Dispersive X-ray spectroscopy (EDS) and electron energy loss spectroscopy (EELS) analyses were also performed in the TEM instrument.

TEM images of the sample withdrawn after 50 nun (Figure 1) shows that most particles are dense Si particles with a surface oxide layer, and some particles are hollow shells. TEM images of the sample withdrawn after 200 min (Figure 2) shows that most particles consist of a shell of oxidized Si and are hollow on the inside. Some few particles are still dense (higher contrast).

There are more dense particles in the sample withdrawn after 50 min more hollow silica spheres in the sample withdrawn after 200 min immersion.

Example 2: Preparation of hollow silica spheres after I) air oxidation to form Si02 shell, and 2) dissolution of Si core at pH 8 The experiment was performed as in Example I, but a Tris buffer solution of pH 8.0 was used instead of PBS. TEM analysis was done as described in Example 1.

TEM images with EDS and EELS of the sample (Figure 3) shows that the major portion of particles consist of hollow silica spheres.

Claims

Claims 1. A process for the production of hollow particles from coated elemental silicon particles, wherein said elemental silicon particles are reacted with water.
2 The process as claimed in claim I for the production of hollow oxidized silicon particles from coated silicon particles comprising elemental silicon, wherein said elemental silicon particles are reacted with water
3 The process as claimed in claim 2, wherein the process comprises the following steps: (i) Elemental silicon particles are oxidized at the surface by oxygen or air; (ii) The particles produced in step (i) are suspended and stirred in water with pH 7 or above until no more hydrogen gas is released from the suspension; (iii)The formed hollow particles are used directly or isolated and dried.
4 The process as claimed in claim 1 for the production of hollow coated silicon particles from coated silicon particles comprising elemental silicon, wherein said elemental silicon particles are reacted with water.
5. The process as claimed in claim 4, wherein the process comprises the following steps: (i) Elemental silicon particles are oxidized at the surface; (ii) The particles produced in step (i) are coated with an inorganic or organic material; (iii) The particles are suspended and stirred in water with pH 7 or above until no more hydrogen gas is released from the suspension; (iv)The formed hollow particles are used directly or isolated and dried.
6 The process as claimed in claim I for the production of hollow coated particles free from silicon from coated silicon particles comprising elemental silicon, wherein said elemental silicon particles are reacted with water.
7. The process as claimed in claim 6 wherein the process comprises die following steps: The particles are coated with an inorganic or organic material; (ii) The particles are suspended and stirred in water with pH 7 or above until no more hydrogen gas is released from the suspension; (iii) The formed hollow particles are used directly or isolated and dried.
8. The process as claimed in any of the claims 3, 5 or 7 wherein the hollow particles are dried using low pressure plus heat, spray drying or freeze drying.