HIGHLY POROUS MAGNESIUM CARBONATE AND METHOD OF PRODUCTION THEREOF

Abstract

The present invention relates to a highly porous magnesium carbonate and method of production thereof. The method according to the invention provides a way to control the average pore size of the highly porous magnesium carbonate by controlling the agglomeration of CO.sub.2 in a powder formation step in a sol-gel based production process. The method makes it possible to adapt the average pore size to a second material, for example a pharmaceutical compound, to be loaded into highly porous magnesium carbonate. The highly porous magnesium carbonate according to the invention comprises mesopores with an average size in the range 10-30 nm.

Claims

1. A highly porous magnesium carbonate comprising mesopores, characterized in that the average pore size of the mesopores is in the range from 10 nm to 30 nm, and the material has a surface area larger than 120 m.sup.2/g and a total pore volume larger than 0.5 cm.sup.3/g, the surface area and the total pore volume determined from nitrogen adsorption isotherms.

2. The highly porous magnesium carbonate according to claim 1 or, wherein the surface area is larger than 150 m.sup.2/g, and even more preferably larger than 200 m.sup.2/g.

3. The highly porous magnesium carbonate according to claim 1 or, wherein the average pore size of the mesopores is in the range from 13 nm to 22 nm.

4. A combined pharmaceutical compound and drug carrier characterized by the drug carrier being the highly porous magnesium carbonate according to claim 1 or 3 loaded with the pharmaceutical compound.

5. The highly porous magnesium carbonate according to claim 4, wherein the pharmaceutical compound is poorly soluble or a BSC II class drug.

6. The highly porous magnesium carbonate according to claim 5, wherein the pharmaceutical compound is itraconazole.

7. A combined cosmetic compound and carrier characterized by the carrier being the highly porous magnesium carbonate according to claim 1 or 3 loaded with the cosmetic compound,

8. A cosmetic compound comprising the highly porous magnesium carbonate according to claim 1 or 3, and wherein the highly porous magnesium carbonate is provided to absorb excess fat from the skin.

9. A medical compound comprising the highly porous magnesium carbonate according to claim 1 or 3, and wherein the highly porous magnesium carbonate is provided to absorb excess body products, such as pus and/or scab.

10. A highly porous magnesium carbonate according to claim 1, characterized in that the highly porous magnesium carbonate comprising mesopores is suitable for carrying a compound or a plurality of compounds, and the mesopores have been given a specific average pore size associated with critical confinement dimensions characteristic to the compound or compounds to be loaded into the highly porous magnesium carbonate, the critical confinement dimensions being predetermined to decrease the amorphous to crystalline transition of the compound or compounds, whereby the highly porous magnesium carbonate will act as a carrier preventing crystallisation.

11. A method of producing a highly porous magnesium carbonate from magnesium oxide, MgO, the highly porous magnesium carbonate comprising mesopores in a range from 2 to 30 nm the method comprising the main steps of: sol-gel synthesis comprising mixing magnesium oxide and methanol under CO.sub.2 pressure resulting in a first solution; powder formation of the first solution resulting in a wet powder; and degassing the wet powder under flow of a non-reactive gas, characterized by that the step of powder formation comprises selecting an energy/work input process path based on if large or small average pore volume in the final highly porous magnesium carbonate according is wanted, the selection being low energy/work input process path for large average pore size and high energy/work input process path for small average pore size, and perfuming the poweder formation based on the selection as (20:2) if low energy/work input process path was selected, enhance the process of CO.sub.2 molecules forming bubbles by decreasing the evaporation rate of CO2 from the mixture; (20:3) if high energy/work input process path was selected, supress agglomeration of CO.sub.2 molecules into bubbles by means that increases the evaporation rate of CO.sub.2 from the mixture.

12. The method according to claim 11, wherein the agglomeration of CO.sub.2 is controlled by selecting a process temperature from the range ?20 to 80? C., and adapting the amount of work depending on the temperature and selected path.

13. The method according to claim 11 or 12, wherein the step of sol-gel synthesis comprises separating MgO particles from the first solution prior to the powder formation step.

14. The method according to any of claims 11 to 13, wherein the step of degassing comprises a stepwise increase of temperature wherein at each temperature a stable state with regards to gas given of from the powder is achieved before further increase of the temperature.

15. The method according to any of claims 11 to 14, wherein the low energy/work input path was selected to produce highly porous magnesium carbonate comprising mesopores having an average pore size in the range from 10 nm to 30 nm, and the material has a surface area larger than 120 m.sup.2/g and a total pore volume larger than 0.5 cm.sup.3/g, the surface area and the total pore volume determined from nitrogen adsorption isotherms

16. A highly porous magnesium carbonate comprising mesopores suitable for carrying a compound or a plurality of compounds, characterized in that it is produced using the method according to any of claims 9 to 15.

Description

BRIEF DESCRIPTION OF THE FIGURES

[0028] A more complete understanding of the above mentioned and other features and advantages of the present invention will be apparent from the following detailed description of preferred embodiments in conjunction with the appended drawings, wherein:

[0029] FIG. 1 is a flowchart illustrating the steps of the method according to the invention:

[0030] FIG. 2 is a schematic illustration of the composite highly porous magnesium carbonate according to the invention;

[0031] FIG. 3 is a thermogravimetric curve of transparent the highly porous magnesium carbonate according to the invention;

[0032] FIG. 4 is a graph showing the particle size of the particles in the reaction mixture after centrifugation and 24 hours of reaction detected by dynamic light scattering;

[0033] FIGS. 5a-b are graphs showing a) Infrared spectrum of dried transparent highly porous magnesium carbonate according to the invention, and b) Infrared spectrum of the transparent powder heated to 250? C.; under nitrogen atmosphere;

[0034] FIG. 6 shows XPS spectra for Mg.sub.2p and O.sub.1s, for transparent highly porous magnesium carbonate according to the invention, wherein in the Mg.sub.2p spectrum the blue line for the magnesium carbonate fit is completely covered by the black line for the recorded spectrum, indicating an excellent fit;

[0035] FIGS. 7a-d are Infrared spectra of a) transparent reaction mixture, b) gel, c) wet powder and d) dried transparent highly porous magnesium carbonate according to the invention;

[0036] FIGS. 8a-i are (left) N.sub.2 adsorption isotherm and (right) DFT pore size distribution and cumulative pore volume of samples A-G of the highly porous magnesium carbonate according to the invention, the samples are described in Table 2 in the Detailed Description of the Invention;

[0037] FIG. 9 is a schematic illustration of the pore forming mechanism utilized in the method according to the invention;

[0038] FIGS. 10a-c are DSC curves of ITZ loaded transparent highly porous magnesium carbonate according to the invention for the three different concentrations of drug loaded into the samples of the highly porous magnesium carbonate according to the invention with varying average pore sizes as well as for the pure drug;

[0039] FIG. 11 is a graph showing time resolved release in simulated gastric fluid of itraconazole (ITZ) loaded into the highly porous magnesium carbonate according to the invention with average pore sizes of 20 nm (top curve), 13 nm (middle curve) and 5.1 nm (lower curve) as well as dissolution of the pure crystalline drug (bottom curve);

[0040] FIG. 12a-b are SEM-images illustrating how the amorphous material can collapse to a non-porous material under certain circumstances, wherein b) is an enlargement of a).

DETAILED DESCRIPTION OF THE INVENTION

[0041] The highly porous magnesium carbonate according to the invention is a composite material that comprises nanometre-sized MgO parts surrounded by amorphous MgCO.sub.3. The amorphous MgCO.sub.3 comprises mesopores of an average pore size in the range ?2 nm to ?30 nm. The method according to the invention provides a way to control the average size of the mesopores by controlling the gel/powder formation rate in a powder formation step of the synthesis of the highly porous magnesium carbonate.

[0042] The highly porous magnesium carbonate according to the invention is synthesised using an optimised version of the sol-gel synthesis method disclosed in the above discussed reference. The method comprises the main steps of i) sol-gel synthesis resulting in a sol from which superfluous MgO particles could be removed by centrifugation, ii) powder formation typically involving stirring that activates gelling and subsequent wet powder generation and finally iii) degassing under nitrogen flow resulting in optically transparent powder particles referred to as transparent highly porous magnesium carbonate. The method will be described with references to the flowchart depicted in FIG. 1:

[0043] 10. Sol-gel synthesis, comprising the steps of:

[0044] 10.1: mixing magnesium oxide and methanol or ethanol or other alcohols under CO.sub.2 pressure. The CO.sub.2 pressure should be above atmospheric pressure and preferably 1-5 bar.

[0045] 10.2: stirring the mixture until a change in viscosity can be observed. As realized by the skilled person the mixture may be subjected to other types of mechanically work, such as shaking, tumbling and mixing. A typical process time for this step is in the order of 1 to 10 hours at room temperature.

[0046] 10.3: realising CO.sub.2 pressure obtaining a cloudy, yellowish solution.

[0047] 10.4: optionally separating superfluous MgO particles for example by centrifuging at 5000 rpm (4696 g) for 60 minutes to obtain an optically clear, off-white coloured liquid and discarding solid particles. The skilled person may apply other separation methods.

[0048] 20. Powder formation:

[0049] The controlling the agglomeration of CO.sub.2 molecules in the above obtained solution into bubbles should be selected in such a way that agglomeration is supressed if the average size of the mesopores of the resulting highly porous magnesium carbonate should be small as compared to the achievable range of mesopores, and the agglomeration is enhanced if the average size of the mesopores should be large as compared to the achievable range of mesopores, the achievable range of mesopores being ?2 nm-?30 nm. The agglomeration of CO.sub.2 molecules into bubbles is suppressed by any means that increases the evaporation rate of CO.sub.2 from the mixture, for example increasing the temperature of the mixture or by subjecting the mixture to mechanical work such as, but not limited to, stirring, tumbling or shaking. The agglomeration of CO.sub.2 molecules into bubbles is enhanced by any means that decreases the evaporation rate of CO.sub.2 from the mixture, for example lowering the temperature of the mixture or by providing a mechanically undisturbed environment. The useful temperature range in this step is ?20 to 80? C.

[0050] The solution would first thicken into a gel (an alcogel) before breaking up into small, wet powder-like pieces, referred to as wet powder, which is used as an indication that the step is completed.

[0051] Powder formation, comprises the steps of:

[0052] 20:1 Selecting an energy/work input process path based on if large or small average pore size in the final highly porous magnesium carbonate according is wanted. The selection being low energy/work input process path for large average pore size (pore size 10-30 nm), and high energy/work input process path for small average pore size (2-10 nm).

[0053] 20:2 If low energy/work input process path was selected: Enhance the process of CO.sub.2 molecules forming bubbles by decreasing the evaporation rate of CO.sub.2 from the mixture, for example lowering the temperature of the mixture and/or by providing a mechanically undisturbed environment.

[0054] 20:3 If high energy/work input process path was selected: Supressing agglomeration of CO.sub.2 molecules into bubbles is by means that increases the evaporation rate of CO.sub.2 from the mixture, for example increasing the temperature of the mixture and/or by subjecting the mixture to mechanical work such as, but not limited to, stiffing, tumbling or shaking.

[0055] 30. Degassing comprising the steps of:

[0056] Degassing or drying the wet powder need to be done in a controlled manner to preserve the highly porous structure of the magnesium carbonate. For example, to directly heat at an elevated temperature, typically above 150? C., would destroy the porous structure and result in a nonporous magnesium carbonate. The degassing is preferably done stepwise, wherein the temperature is increased stepwise and at each temperature degassing is performed until a stable condition is achieved, with regards to the gas given off. The stable condition could be determined by monitoring the weight of the wet powder and not increase the temperature until the weight decrease diminish, observe the rate of the gas given off, or by testing out an appropriate drying scheme by analysing the resulting magnesium carbonate. Alternatively, a continuous increase of the degassing temperature could be utilized, given that the continuous increase is careful enough. Given the knowledge that the degassing needs to be carefully controlled in order to preserve the highly porous nature of the magnesium carbonate, the skilled person may design an appropriate degassing scheme. The degassing should be performed under a slow flow, typically at ?20 cm.sup.3/minute, of a non-reactive gas, i.e. not reacting with the compounds in the wet powder. Nitrogen is a preferred choice of a non-reacting gas.

[0057] A preferred degassing scheme comprises the substeps of:

[0058] 30.1: degassing the wet powder under a slow flow of nitrogen. Typically at ?20 cm.sup.3/minute at 50-100? C. for at least 1 hour.

[0059] 30.3: further degassing the wet powder at 100-200? C. for at least 1 our under a slow flow of nitrogen (?20 cm.sup.3/minute).

[0060] 30.3 sub step of a heat treatment and at 200-350? C. for at least 1 hour under a slow flow of nitrogen (?20 cm.sup.3/minute). The resulting powder is optically transparent and is referred to as transparent highly porous magnesium carbonate.

[0061] In the step of controlling agglomeration (20:1) subjecting the mixture to mechanical work can be done in various ways. In the process described below as a non-limiting example, stirring the solution obtained in the sol-gel synthesis step is done at 60-100 rpm in a ventilated area. Appropriate speed and duration will depend on for example size and shape of the reactor vessel, the stirring gear etc. In similar way may the parameters need adjustments if other means of subjecting the solution to mechanical work is used, for example shaking, tumbling, vibrating etc. The skilled persons will, with guidance from the method according to the invention and from the discussion presented below about the agglomeration and pore formation, be able to choose a suitable means for controlling the agglomeration to produce the desired average pore size. Such variations are considered to be within the scope of the present application.

[0062] The method according to the present invention makes it possible to produce a composite highly porous magnesium carbonate comprising particles comprising MgO and amorphous magnesium carbonate parts, as shown by DLS, XPS, TGA and elemental analysis, with mesopores whose average size could be controlled from ?2 nm to ?30 nm. The composite highly porous magnesium carbonate according to the invention is schematically depicted in FIG. 2. A plurality of nanometre-sized MgO parts 205 and to them associated amorphous magnesium carbonate 210 form ring-like or shell-like structures 215. The mesopores, with a size in the range 10-30 nm, 220 are formed by a plurality of the shell-like structures 215. The mesopores 220 can be seen as remains of the agglomerated CO.sub.2 bubbles discussed in the powder formation step, 20.

[0063] The method of the invention may, apart from producing highly porous magnesium carbonate also be used to produce highly porous carbonates of calcium and nickel, or mixtures thereof. As appreciated by the skilled person different starting materials need to be used and adaptions with regards to the process parameters may be required.

[0064] The ability to control the pore size of the highly porous magnesium carbonate opens up new possibilities in tailoring the material for certain applications, for examples in applications wherein the highly porous magnesium carbonate is a carrier of a second material or compound, and in applications Wherein a certain pore size can be associated to absorption, separation or purification properties. Of particular interest are drug delivery applications wherein the highly porous magnesium carbonate is loaded with a pharmaceutical compound, a drug, or a combination of drugs, Both large and small pores can be of interest.

[0065] Certain compounds have enhanced pharmaceutical effect associated with the compound being in an amorphous phase since the in vivo bioavailability owing to the low dissolution rate of the crystalline form of the drug is low in the gastrointestinal fluids following oral administration. The transition to a crystalline, and less effective phase, can be hindered or at least delayed, if the compound is confined to dimensions that are characteristic to the drug compound, typically below 10-20 nm. By loading the drug into a highly porous magnesium carbonate which has been given a specific average pore size associated with the characteristic dimensions of the drug compound, the highly porous magnesium carbonate will act as a carrier that prevents crystallisation of the drug. It should be noted that the specific average pore size does not necessarily need to match the size of the drug molecule. Rather, a suitable pore size hindering the crystallisation needs to be determined for a specific drug compound and its intended application, such testing being possible thanks to the method and highly porous magnesium carbonate according to the invention. It is often advantageous to use a material with as large pore size as possible, that still prevents crystallisation, in order to reach high loading degrees. One example, representing one embodiment of the invention, of how to determine a suitable average pore size to prevent crystallisation is given below for the drug itraconazole.

[0066] One embodiment of the invention is a highly porous magnesium carbonate wherein the average pore size is adapted to relate to a critical confinement size of a compound to be loaded into the highly porous magnesium carbonate, the confinement size relating to dimensions at which or below crystallisation is hindered or delayed. Drug delivery is an obvious implementation of this embodiment of the invention, but also other applications wherein a transition of the loaded compound can be controlled or hindered by the pore size of the highly porous magnesium carbonate, may be envisaged. :A large pore size combined with a large surface area and a high total pore volume is also important for applications utilizing adsorption, for example gas adsorption, and applications utilizing release of active compounds for example fragrances that first are adsorb by the highly porous material and then released or wherein the highly porous material is combined with a surface active agent. One further example is in skin care wherein a cosmetic compound comprising the highly porous magnesium carbonate can be used to absorb excess fat (sebum) from the skin.

[0067] A highly porous magnesium carbonate prepared according to the above described method of the invention contained about 10-20 wt. % MgO (and 80-90 wt. % MgCO.sub.3) as determined by CHN elemental analysis, inductively coupled plasma optical emission spectrometry (ICP-OES) and thermogravimetric analysis (TGA) as illustrated in FIG. 3 and table 1. FIG. 3 is a graph showing a thermogravimetric curve of transparent highly porous magnesium carbonate, the sample weight at 350? C. and 500? C. were used to back-calculate the MgO content of the starting material. The calculated oxide content using the TGA data was ?13.8 wt %. This gave a stoichiometric MgO content of the transparent powder of around 30-50 mol %. This portion of MgO could not be removed by centrifugation at 4969 g.

TABLE-US-00001 TABLE 1 Elemental composition and MgO content (from CHN/ICP-OES and TGA) of the transparent highly porous magnesium carbonate, oxygen analysis was not possible using ICP due to the high metal content. MgO wt. % MgO wt. % C H N Mg (from CHN/ICP) (from TGA) Wt. % 10.80 0.28 <0.01 26.2 17.6 13.8

[0068] Nanometer-sized aggregates of around 50-100 nm in diameter were detected in the sol described above in the synthesis of highly porous magnesium carbonate using Dynamic Light Scattering (DLS), FIG. 4, Significant growth of these nanoparticles occurred with time when the reaction mixture was covered and left standing at room temperature (i.e. without active evaporation/drying). After 2 hours, the nanoparticles became too large to be detected by DLS. The observed particle growth most likely stems from aggregation of particles. CHN analysis, Inductively Coupled Plasma-Optical Emission Spectroscopy (ICP-OES), Thermogravimetric analysis (TGA), X-ray photoemission spectroscopy (XPS) and IR spectroscopy showed that these nanoparticles were composed of MgCO.sub.3 and MgO. Since the highly porous magnesium carbonate is X-ray amorphous, it was concluded that the MgO that is comprised in the material was in the form of small (too small to be detected by powder XRD) nanometer-sized particles surrounded by amorphous MgCO.sub.3. Hence, the highly porous magnesium carbonate can be seen as composite material.

[0069] An IR spectrum of the transparent highly porous magnesium carbonate showed that the IR bands related to MgCO.sub.3 were present, see FIG. 5a-b. The Mg.sub.2p and O.sub.1s XPS spectra of the powder, FIG. 6a-b, showed that the surface of the powder particles contained mainly MgCO.sub.3 and a small amount of MgO. The transparent highly porous magnesium carbonate presented in this study contained a much lower level of MgO than the samples presented in U.S. Pat. No. 9,580,330 due to the optional separating step 10:4.

[0070] A discussion of the formation mechanism of the highly porous magnesium carbonate is given below. The discussion is given for illustrative purposes only and should be considered as a non-limiting framework presented in order to further help the skilled person to tailor the material to specific implementations. The results indicate that the material is formed by aggregation of nanometre-sized MgCO.sub.3/MgO composite particles, which will be discussed in detail below. The nanometre-sized composite particles are formed during the reaction between MgO, methanol and CO.sub.2. It has been shown previously that MgO is practically insoluble in methanol (solubility ?0.1%). The low solubility of MgO in methanol was also observed in this work, as indicated by an intense white cloudy mixture when the two were mixed. Interestingly, when the reaction vessel was pressurized with CO.sub.2 (4 bar) for 24 hours, the mixture became noticeably less cloudy. The reaction mixture became light yellow and only slightly cloudy, as observed earlier. After centrifugation, the reaction mixture is an optically clear, yellow solution. Tyndall scattering can be observed by shining a red laser light through the solution, indicating the presence of nanoparticles. As explained above, these nanoparticles appeared to be composites of MgO/MgCO.sub.3.

[0071] The pore size distributions of materials synthesized using the different powder forming conditions outlined in Table 2 were obtained by density functional theory (DFT) analysis of N.sub.2 sorption isotherms as shown in the graphs of FIG. 8a-i. The surface area was determined by using the well-recognized BET analysis of nitrogen sorption isotherms. The analysis method hereinafter referred to as the BET method. These transparent samples of highly porous magnesium carbonate were prepared using various powder formation conditions as detailed in Table 2. The table also summarizes the pore properties of the different materials showing that transparent magnesium carbonate powder could be made with very different pore sizes in a controlled manner. Sample I was produced with ethanol as the reaction liquid.

TABLE-US-00002 TABLE 2 Power formation temperatures, specific surface area and pore properties of different samples. Mechanical stirring was used to form the gel and the powder for all samples except for sample D. Powder formation Peak DFT Total pore temperature Surface area pore size volume Sample (? C.) (m.sup.2/g) (nm) (cm.sup.3/g) A ?20 263 ~13 1.27 B 10 297 ~10 1.15 C 20 499 ~6.5 0.97 D 20 (no stirring) 173 ~20 1.00 E 30 618 ~5.1 0.76 F 50 661 ~3.4 0.60 G 80 690 ~2.9 0.50 H RT 149 ~20 0.80 I RT 225 ~22 1.55

[0072] The average size of the mesopores could be controlled from ?3 nm to ?30 nm by adjusting the gel/powder formation rate in the powder formation step, 20 of the synthesis (FIG. 1). If the low energy/work input process path 20:2 was selected, mesopores could be formed in the range from ?10 nm to ?30 nm. If the approach of low energy/work input is taken to the extreme, i.e. leaving the sol-gel solution in step 20 undisturbed for a long time (several days) at a low or moderate temperature the results in a collapse of the porous structure a non-porous X-ray amorphous magnesium carbonate material is formed. Even magnesite (MgCO.sub.3) crystals may form inside the gel. A material with a collapsed porous structure is depicted in FIG. 12a-b.

[0073] FIG. 9 is a schematic illustration of how the pores in the material are formed. FIG. 9 also shows how the pore size can be controlled by controlling the agglomeration of CO.sub.2 molecules into bubbles during the powder formation step of the synthesis. During this step, a large amount of CO.sub.2 is given off. The eliminated gas phase CO.sub.2 molecules need to travel to the liquid/air interface between the reaction mixture/gel and ambient air before evaporating from the reaction mixture into gas phase. However, when inside the reaction mixture, the CO.sub.2 molecules aggregate to form bubbles. Nanometre-sized particles (MgCO.sub.3/MgO composites) assemble around these CO.sub.2 bubbles which are then essentially trapped in this configuration. The average size of the bubble renders the average pore size of the material. Low temperature allows CO.sub.2 molecules to form aggregates in the reaction mixture at a higher extent than at high temperature (due to slower kinetics). The slow kinetics results in large bubbles and subsequently large pores. Sample D (Table 2) demonstrated the effect of reduced energy input (by eliminating stirring) clearly, as it has the largest pore size of the synthesized samples in this study. The lower path in the FIG. 9 illustrated the formation process at lower temperatures and the upper path at higher temperatures.

[0074] After the wet powder forms, the pores need to be fixed by heating under N.sub.2 flow in a carefully controlled way as described in the degassing step 30. This step fixes the shape of the assembled powder particles and removes the trapped CO.sub.2 bubbles, resulting in a porous solid.

[0075] The impact of being able to control pore size of the synthesized material can be shown by its ability to stabilize amorphous compounds and the tailored drug release profile. The drug itraconazole (ITZ) was loaded into transparent highly porous magnesium carbonate samples according to the invention (the drug carrier) with three different average pore sizes (Sample E. A and D with average pore sizes of ?5.1 nm, ?13 nm and ?20 nm, respectively). ITZ, in its crystalline form, is a poorly water-soluble antifungal agent

[0076] Differential scanning calorimetry (DSC) was employed to analyze the structure of ITZ loaded into the pores of the carrier as illustrated in FIG. 10a-c. TGA was used to confirm the concentration of drug loaded. The described drug loading procedures resulted in the different carrier samples being loaded with 30, 45 and 60 wt % of ITZ. An endothermic peak at 169? C. was observed in the DSC curve for the pure drug. This peak corresponds to the melting point of crystalline ITZ. For all carrier samples loaded with an ITZ concentration corresponding to 30 wt %, this endothermic peak was absent. The lack of such peak confirmed that all carrier samples were able to completely suppress crystallization of the drug loaded inside the pores. The complete lack of endothermic peaks at this degree of loading also indicates that only an insignificant, if any, amount of ITZ resides on the outer surface of the carrier particles. The outer surface area of the carrier particles is negligible compared to the internal surface area and only has a limited ability to interact with the ITZ in order to suppresses the crystallization of the substance. When the drug loading level increased, crystallization was no longer completely suppressed, irrespectively to the sample identity. Whereas samples E (pore size ?5.1 nm) and A (pore size ?13 nm) were able to completely stabilize ITZ in the amorphous state at a drug loading degree of 45 wt %, a weak and broad endothermic peak located at the melting point temperature of crystalline ITZ was detected for Sample D (pore size ?20 nm). Similar humps were observed for all samples at drug loading degrees of 60 wt %. This illustrates that large pore sizes offer more space for the incorporated drug molecules of small size (having the rectangular cuboid dimensions of 2.97 nm?0.93 nm?0.69 nm) to rearrange and crystallize. Furthermore, the finding also emphasized that for optimized stabilization effect of the drug, the pore size of the drug carrier must correlate to the size of the drug. The samples with 5.1 and 13 nm average pores size could host relatively high amounts of ITZ and successfully hindered the crystallization of ITZ (low solubility form of the substance). Since ITZ remained amorphous in all samples at a loading degree of 30 wt %, this degree of drug loading was used for the drug release measurements.

TABLE-US-00003 TABLE 3 DSC analysis of highly porous magnesium carbonate according to the invention with different average pore sizes loaded with different amounts of itraconazole. Average pore size 30% 45% 60% (nm) loading loading loading Sample D ~20 amorphous Semi- Semi- crystalline crystalline Sample A ~13 amorphous amorphous Semi- crystalline Sample E ~5.1 amorphous amorphous Semi- crystalline

[0077] The time-resolved release of ITZ from the grounded transparent carrier particles into simulated gastric fluid (pH ?1.3) is shown in FIG. 11, using highly porous magnesium carbonate with average pore sizes of 20 nm (top curve), 13 nm (middle curve) and 5.1 nm (lower curve) as well as dissolution of the pure crystalline drug (bottom curve). The lines are drawn as guides for the eye. The error bars signify variations over three measurements. As observed in the figure, the release rate during the first 30 minutes can be enhanced with a factor of ?23 (release from Sample D as compared to pure ITZ) when ITZ was loaded into the transparent highly porous magnesium carbonate. The corresponding release rate enhancement for samples A and E were ?17 and ?13, respectively. During the first 30 minutes of release, no visible changes to the powder in the dissolution vessel were observed.

[0078] After a few hours, powder dissolution was observed. This was expected due to the acidic conditions in the release medium. The results showed clearly that the amorphous phase stabilization properties, as well as the release rate, can be tuned by adjusting the pore size of the carrier. This finding opens up for new possibilities to stabilize the vast number of amorphous compounds which are utilized as drugs or potential drug candidates. It should be noted that both MgCO.sub.3 and MgO are GRAS (Generally Recognized as Safe) listed by the U.S. Food and Drug Administration and have E-numbers (E504 for magnesium carbonate and E530 for magnesium oxide).

[0079] In many applications, medical as well as other, a large pore size, i.e. larger than 10 nm, together with a high surface area and the possibility to receive a high percentage of the substance to be loaded in the porous material, is highly sought for. The highly porous magnesium carbonate according to the invention with pore size in the range 10 nm to 30 nm and with a surface area larger than 120 m.sup.2/g and a total pore volume larger than 0.5 cm.sup.3/g, combine providing large pores with the ability of a loading degree, samples A, B, D, H, I. For example, sample A with a surface area of 263 m.sup.2/g, a pore size of 13 nm and an initial total pore volume of 1.27 cm.sup.3/g, had a remaining total pore volume of 0.59 cm.sup.3/g, or 54%, after being loaded with 30 wt % itraconazole. As a comparison a highly porous magnesium carbonate prepared according to U.S. Pat. No. 9,580,330 with 13 nm pores, a surface area of 77 m.sup.2/g, and an initial total pore volume of 0.46 cm3/g, had a total pore volume of 0.20 cm.sup.3/g, or 43% after being loaded with 30 wt % itraconazole.

[0080] In one embodiment of the invention the method of producing the highly porous magnesium carbonate comprising mesopores is optimized for resulting in large pores, i.e. 10-30 nm and a surface area >120 m.sup.2/g and a total pore volume >0.5 cm.sup.3/g, the surface area and total pore volume determined from nitrogen sorption isotherms. In the powder formation step, step 20, the agglomeration of CO.sub.2 molecules into bubbles is enhanced by any means that decreases the evaporation rate of CO.sub.2 from the mixture, for example lowering the temperature of the mixture or by providing a mechanically undisturbed environment, or with very little disturbance such as gentle stirring. Given the knowledge of how energy input in any form (heating, mechanical work etc) affect the pore size, the skilled person is capable of designing the process step of powder formation to achieve the intended result.

[0081] An embodiment of the invention is a highly porous magnesium carbonate comprising mesopores with an average size in the range of 10-30 nm and surface area larger than 120 m.sup.2/g, more preferably the surface area is larger than 150 m.sup.2/g, and even more preferably larger than 200 m.sup.2/g, a total pore volume larger than 0.5 cm.sup.3/g, the surface area and the total pore volume determined from nitrogen adsorption isotherms.

[0082] The large pore material according to the invention is particularly interesting as a carrier for pharmaceutical compounds displaying poor solubility, for example drugs categorized in the BCS (Biopharmaceutics Classification System) class II. BCS was introduced as a classification system in 2000, it classifies drug substances based on permeability and solubility. BCS class II are substances with high permeability (>90% after administrated dose) and low solubility (the highest dose can not be dissolved in 250 ml water at pH 1-7.5 and 37 C).

[0083] According to one embodiment of the invention a combined pharmaceutical compound and a drug carrier comprising the highly porous magnesium carbonate is provided. For poorly soluble pharmaceutical compounds or compounds belonging to the BCS class II, the highly porous magnesium carbonate should preferably be the large pore material with average pore size in the size range 10-30 nm. A larger pore size is associated with a larger pore volume, which enables a higher loading degree.

[0084] According to one embodiment of the invention a cosmetic compound is provided comprising the highly porous magnesium carbonate according to the invention. The highly porous magnesium carbonate is provided to absorb excess fat, sebum, from the skin.

[0085] Absorption of excess products from the body could be envisaged also for medical purposes, for example in wound healing, wherein the highly porous magnesium carbonate is provided to absorb for example pus and/or scab. According to one embodiment of the invention a medical compound is provided comprising the highly porous magnesium carbonate according to the invention.