Mesoporous Magnesium Carbonate Research Articles

Crosslinking ionic oligomers sol-gel synthesis of high-surface-area mesoporous magnesium carbonate and its general applicability

Mesoporous magnesium carbonate has been widely used in controlled release of drugs, adsorption or catalysis. In traditional methods, expensive alkoxide or MgO are usually employed as Mg-source to prepare mesoporous magnesium carbonate. Herein, based on the crosslinking property of ionic oligomers, a novel crosslinking ionic oligomer sol-gel method was proposed to prepare high-surface-area mesoporous magnesium carbonate using cheap MgCl2·6H2O and CO2 as material. (MgCO3)n crosslinking oligomer sols was produced based on the H-bond capping effects of ethanol and triethylamine. The evolution mechanism of crosslinking (MgCO3)n oligomer sols to gels was studied by using ATR-FTIR and NMR. The results indicated that with the slow volatilization of ethanol and triethylamine, a part of H-bond disappeared, which initiating the chain growth of (MgCO3)n oligomer molecules, and finally forming a crosslinking network. Combined with a CO2 critical point drying process, amorphous mesoporous magnesium carbonate nanoparticle with high surface area was obtained and characterized using ATR-FTIR, XRD, XPS, nitrogen adsorption/desorption analysis, SEM, TEM and EDS systematically. The specific surface area of magnesium carbonate reached 628 m2 g−1 when the n(TEA)/n(Mg2+) was 40:1. Moreover, the general applicability of this method was verified. Mesoporous sulfate and phosphate were synthesized, which indicating the crosslinking oligomer sol-gel chemistry provided a general strategy for the construction of mesoporous inorganic oxysalt materials. Our work has important guiding significance for the preparation of other mesoporous materials that using cheap inorganic salt as raw material.

Development of a simple paste for 3D printing of drug formulations containing a mesoporous material loaded with a poorly water-soluble drug

Poorly soluble drugs represent a substantial portion of emerging drug candidates, posing significant challenges for pharmaceutical formulators. One promising method to enhance the drug’s dissolution rate and, consequently, bioavailability involves transforming them into an amorphous state within mesoporous materials. These materials can then be seamlessly integrated into personalized drug formulations using Additive Manufacturing (AM) techniques, most commonly via Fused Deposition Modeling. Another innovative approach within the realm of AM for mesoporous material-based formulations is semi-solid extrusion (SSE). This study showcases the feasibility of a straightforward yet groundbreaking hybrid 3D printing system employing SSE to incorporate drug-loaded mesoporous magnesium carbonate (MMC) into two different drug formulations, each designed for distinct administration routes. MMC was loaded with the poorly water-soluble drug ibuprofen via a solvent evaporation method and mixed with PEG 400 as a binder and lubricant, facilitating subsequent SSE. The formulation is non-aqueous, unlike most pastes which are used for SSE, and thus is beneficial for the incorporation of poorly water-soluble drugs. The 3D printing process yielded tablets for oral administration and suppositories for rectal administration, which were then analyzed for their dissolution behavior in biorelevant media. These investigations revealed enhancements in the dissolution kinetics of the amorphous drug-loaded MMC formulations. Furthermore, an impressive drug loading of 15.3 % w/w of the total formulation was achieved, marking the highest reported loading for SSE formulations incorporating mesoporous materials to stabilize drugs in their amorphous state by a wide margin. This simple formulation containing PEG 400 also showed advantages over other aqueous formulations for SSE in that the formulations did not exhibit weight loss or changes in size or form during the curing process post-printing. These results underscore the substantial potential of this innovative hybrid 3D printing system for the development of drug dosage forms, particularly for improving the release profile of poorly water-soluble drugs.

Metronidazole and Ketoprofen-Loaded Mesoporous Magnesium Carbonate for Rapid Treatment of Acute Periodontitis In Vitro.

In the clinical pharmacological treatment of acute periodontitis, local periodontal administration is expected to be preferable to systemic administration. However, the action of the active medicine component is hindered and diminished by the limitation of drug solubility, which does not provide timely relief of the enormous pain being suffered by patients. This study aimed to develop a mesoporous magnesium carbonate (MMC) medicine loading system consisting of MMC, metronidazole (MET), and ketoprofen (KET), which was noted as MET-KET@MMC. A solvent evaporation process was utilized to load MET and KET in MMC. Scanning electron microscopy, nitrogen sorption, thermogravimetric analysis, and X-ray diffraction were performed on the MET-KET@MMC. The rapid drug release properties were also investigated through the drug release curve. The rapid antiseptic property against Porphyromonas gingivalis (P. gingivalis) and the rapid anti-inflammatory property (within 1 min) were analyzed in vitro. The cytotoxicity of MET-KET@MMC was tested in direct contact with human gingival cells and human oral keratinocytes. Crystallizations of MET and KET were completely suppressed in MMC. As compared to crystalline MET and KET, MMC induced higher apparent solubility and rapid drug release, resulting in 8.76 times and 3.43 times higher release percentages of the drugs, respectively. Over 70.11% of MET and 85.97% of KET were released from MMC within 1 min, resisting bacteria and reducing inflammation. MET-KET@MMC nanoparticles enhanced the solubility of drugs and possess rapid antimicrobial and anti-inflammatory properties. The MET-KET@MMC is a promising candidate for the pharmacotherapy of acute periodontitis with drugs, highlighting a significant clinical potential of MMC-based immediate drug release systems.

Processability of mesoporous materials in fused deposition modeling for drug delivery of a model thermolabile drug

The incorporation of drug-loaded mesoporous materials in dosage forms prepared with fused deposition modeling (FDM) has shown the potential to solve challenges relating to additive manufacturing techniques, such as the stability of poorly-soluble drugs in the amorphous state. However, the addition of these non-melting mesoporous materials significantly affects the mechanical properties of the filament used in FDM, which in turn affects the printability of the feedstock material. Therefore, in this study a full-factorial experimental design was utilized to investigate different processing parameters of the hot melt extrusion process, their effect on various mechanical properties and the potential correlation with the filaments' printability. The thermolabile, poorly-soluble drug ibuprofen was utilized as a model drug to assess the potential of two mesoporous materials, Mesoporous Magnesium Carbonate (MMC) and a silica-based material (MCM-41), to thermally protect the loaded drug. Factorial and principal components analysis displayed a correlation between non-printable MCM-41 filaments and their mechanical properties where printable filaments had a maximum stress >7.5 MPa and a Young's modulus >83 MPa. For MMC samples there was no clear correlation, which was in large part attributed to the filaments' inconsistencies and imperfections. Finally, both mesoporous materials displayed a thermal protective feature, as the decomposition due to the thermal degradation of a significant portion of the thermolabile drug was shifted to higher temperatures post-loading. This highlights the potential capability of such a system to be implemented for thermosensitive drugs in FDM applications.

Bioavailability of Celecoxib Formulated with Mesoporous Magnesium Carbonate-An In Vivo Evaluation.

An attractive approach to increase the aqueous apparent solubility of poorly soluble drugs is to formulate them in their amorphous state. In the present study, celecoxib, a poorly soluble drug, was successfully loaded into mesoporous magnesium carbonate (MMC) in its amorphous state via a solvent evaporation method. Crystallization of celecoxib was suppressed, and no reaction with the carrier was detected. The MMC formulation was evaluated in vitro and in vivo in terms of oral bioavailability. Celebra®, a commercially available formulation, was used as a reference. The two celecoxib formulations were orally administrated in male rats (average of n = 6 animals per group), and blood samples for plasma were taken from all animals at different time points after administration. There was no statistical difference (p > 0.05) in AUCinf between the two formulations. The results showed that MMC may be a promising drug delivery excipient for increasing the bioavailability of compounds with solubility-limited absorption.

Bioavailability of Celecoxib Formulated with Mesoporous Magnesium Carbonate – an in Vivo Evaluation

Bioavailability of Celecoxib Formulated with Mesoporous Magnesium Carbonate – an in Vivo Evaluation

Increasing the Transport of Celecoxib over a Simulated Intestine Cell Membrane Model Using Mesoporous Magnesium Carbonate.

In the current work, mesoporous magnesium carbonate (MMC) was used to suppress crystallization of the poorly soluble drug celecoxib (CXB). This resulted in both a higher dissolution rate and supersaturation of the substance in vitro as well as an increased transfer of CXB over a Caco-2 cell membrane mimicking the membrane in the small intestine. The CXB flux over the cell membrane showed a linear behavior over the explored time period. These results indicate that MMC may be helpful in increasing the bioavailability and obtaining a continuous release of CXB, and similar substances, in vivo. Neusilin US2 was used as a reference material and showed a more rapid initial release with subsequent crystallization of the incorporated CXB in the release media. The presented results form the foundation of future development of MMC as a potential carrier for poorly soluble drugs.

3D-Printed Mesoporous Carrier System for Delivery of Poorly Soluble Drugs.

Fused deposition modelling (FDM) is the most extensively employed 3D-printing technique used in pharmaceutical applications, and offers fast and facile formulation development of personalized dosage forms. In the present study, mesoporous materials were incorporated into a thermoplastic filament produced via hot-melt extrusion and used to produce oral dosage forms via FDM. Mesoporous materials are known to be highly effective for the amorphization and stabilization of poorly soluble drugs, and were therefore studied in order to determine their ability to enhance the drug-release properties in 3D-printed tablets. Celecoxib was selected as the model poorly soluble drug, and was loaded into mesoporous silica (MCM-41) or mesoporous magnesium carbonate. In vitro drug release tests showed that the printed tablets produced up to 3.6 and 1.5 times higher drug concentrations, and up to 4.4 and 1.9 times higher release percentages, compared to the crystalline drug or the corresponding plain drug-loaded mesoporous materials, respectively. This novel approach utilizing drug-loaded mesoporous materials in a printed tablet via FDM shows great promise in achieving personalized oral dosage forms for poorly soluble drugs.

Mesoporous magnesium carbonate for use in powder cosmetics.

ObjectiveIn the present study, we describe the features and functional properties of a new powder cosmetic ingredient, an amorphous mesoporous magnesium carbonate (MMC, also named Upsalite®) with regard to physical characteristics as well as functional attributes.MethodsPhysical and functional characterization of MMC, as compared to other common powder cosmetic ingredients (silica, mica, kaolin, talc and starch), was assessed using nitrogen gas adsorption, powder X‐ray diffraction, particle size distribution by laser diffraction, scanning electron microscopy (SEM), and oil and moisture uptake tests. The powder ingredients were also applied on human skin and analysed for short‐ and long‐term mattifying effect, and a new method was developed to measure flashback effect. MMC was tested for skin irritation using an in vitro cell model as well as in vivo, through the Human Repeated Insult Patch Test on 50 human volunteers.ResultsMesoporous magnesium carbonate has a high surface area and pore volume. It has an excellent absorption capacity and can take up both oil and water simultaneously. It provides instant and long‐lasting mattifying effect when applied on human skin without drying or irritating skin and exhibits no measured flashback effect.ConclusionMesoporous magnesium carbonate has good sensory and visual characteristics as well as excellent absorbing and mattifying properties, suggesting that it has great potential to replace other powder ingredients currently used as fillers and absorbers in powder cosmetics.

In Vitro Performance and Chemical Stability of Lipid-Based Formulations Encapsulated in a Mesoporous Magnesium Carbonate Carrier.

Lipid-based formulations can circumvent the low aqueous solubility of problematic drug compounds and increase their oral absorption. As these formulations are often physically unstable and costly to manufacture, solidification has been suggested as a way to minimize these issues. This study evaluated the physicochemical stability and in vitro performance of lipid-loaded mesoporous magnesium carbonate (MMC) particles with an average pore size of 20 nm. A medium chain lipid was loaded onto the MMC carrier via physical adsorption. A modified in vitro lipolysis setup was then used to study lipid release and digestion with 1H nuclear magnetic resonance spectroscopy. The lipid loading efficiency with different solidification techniques was also evaluated. The MMC, unlike more commonly used porous silicate carriers, dissolved during the lipolysis assay, providing a rapid release of encapsulated lipids into solution. The digestion of the dispersed lipid-loaded MMC therefore resembled that of a coarse dispersion of the lipid. The stability data demonstrated minor degradation of the lipid within the pores of the MMC particles, but storage for three months did not reveal extensive degradation. To conclude, lipids can be adsorbed onto MMC, creating a solid powder from which the lipid is readily released into the solution during in vitro digestion. The chemical stability of the formulation does however merit further attention.

Exploring the Use of Amine Modified Mesoporous Magnesium Carbonate for the Delivery of Salicylic Acid in Topical Formulations: In Vitro Cytotoxicity and Drug Release Studies.

Salicylic acid (SA) has for a long time been used to treat various skin disorders due to its anti-inflammatory, bacteriostatic, and antifungal properties. In the present work, mesoporous magnesium carbonate (MMC), a promising drug carrier, was modified with 3-aminopropyl-triethoxysilane to enable loading of SA. The amine modified MMC (aMMC) was successfully loaded with 8 wt.% of SA via a solvent evaporation method. SA was later completely released from the carrier in less than 15 min. Furthermore, the cytotoxicity of the functionalized material was evaluated. aMMC was found to be non-toxic for human dermal fibroblast cells with particle concentration of up to 1000 µg/mL when exposed for 48 h. The presented results form the basis of future development of aMMC as a potential carrier for SA in dermatological applications.

Amorphous Mesoporous Magnesium Carbonate as a Functional Support for UV-Blocking Semiconductor Nanoparticles for Cosmetic Applications

Highly porous amorphous mesoporous magnesium carbonate (MMC) with a Brunauer–Emmett–Teller (BET) surface area over 600 m2·g–1 was evaluated as a micrometer-sized support for TiO2 and ZnO semiconduc...

Amine-Modified Mesoporous Magnesium Carbonate as an Effective Adsorbent for Azo Dyes

Mesoporous magnesium carbonate (MMC) was evaluated as a potential candidate material for removal of dyes from textile industry wastewater. The adsorption property of MMC was analyzed for three different azo dyes: reactive black 5 (RB5), amaranth (AM), and acid red 183 (AR183). Further, the effect of porosity, amine modification, ionic strength, and pH was evaluated. MMC modified with 3-(aminopropyl)triethoxysilane (aMMC) showed consistently high uptake levels for all of the azo dyes tested; the uptake of RB5, AM, and AR183 was ∼360, ∼143 and ∼170 mg/g, respectively. The results demonstrated the importance of porosity and surface chemistry in the effective adsorption of the azo dye in aqueous systems. The uptake of RB5 and AM on aMMC was not significantly affected by pH (when varied between 4 and 10), although reduced uptake of RB5 and AM was observed at pH values <2 and >12. The addition of NaCl salt at concentrations up to 1000 mM had minimal effect on the high uptake of RB5 on aMMC. The uptake of AM by aMMC was reduced by approximately 20% in the presence of NaCl even at low concentrations. The uptake of AR183 by aMMC varied noticeably by changes in pH and no specific trend was observed. The presence of NaCl also adversely affected the uptake of AR183 on aMMC. The adsorption of the azo dye on aMMC was most likely driven by electrostatic interactions. We show here that aMMC is a potential candidate adsorbent for the effective removal of azo dyes from textile wastewaters.

Carbon dioxide adsorption on mesoporous magnesium carbonate

Mesoporous magnesium carbonate (MMC) was synthesized and tested for its ability to separate CO2 from N2. The pure gas CO2 uptake of MMC was around 1.5 mmol/g at 101 kPa, 0 °C. The N2 uptake under the same conditions was less than 0.1 mmol/g. Al(NO3)3, Al2O3, K2CO3 and KNO3 were introduced into the porous structure of MMC as additives. All of the additives tested increased the CO2 uptake of MMC and increased its selectivity towards CO2. The incorporation of 5 wt.% K2CO3 increased the CO2 uptake of MMC up to over 3.2 mmol/g. The ideally adsorbed solution theory was used to calculate the CO2 selectivity of MMC and MMC with additives for a hypothetical gas mixture that contained 15% CO2: 85% N2. The CO2 selectivity at 101 kPa (0 °C) was around 60. MMC with 5 wt.% K2CO3 had a CO2 selectivity of over 150 under the same conditions. Vacuum swing cyclic CO2 adsorption/desorption showed that the CO2 uptake on MMC with 5 wt.% K2CO3 decreased after each cycle. Heat regeneration (up to 250 °C, for 10 minutes) could recover most of the lost CO2 capacity after each cycle. Heat regeneration indicatively improved the cyclic performance of this adsorbent. MMC with 5 wt.% K2CO3 was the best performing adsorbent in this study and can potentially be further developed into a good CO2 adsorbent for temperature swing adsorption (TSA) processes.

Inorganic carbonate composites as potential high temperature CO2 sorbents with enhanced cycle stability.

A calcium magnesium carbonate composite (CMC) material containing highly porous amorphous calcium carbonate (HPACC) and mesoporous magnesium carbonate (MMC) was synthesized. CMCs with varying HPACC : MMC mol ratios and high BET surface area (over 490 m2 g−1) were produced. The CMCs retained the morphology shared by HPACC and MMC. All these materials were built up of aggregated nanometer-sized particles. We tested the CO2 uptake properties of the synthesized materials. The CMCs were calcined at 850 °C to obtain the corresponding calcium magnesium oxide composites (CMOs) that contained CaO : MgO at different mol ratios. CMO with CaO : MgO = 3 : 1 (CMO-3) showed comparable CO2 uptake at 650 °C (0.586 g g−1) to CaO sorbents obtained from pure HPACC (0.658 g g−1) and the commercial CaCO3 (0.562 g g−1). Over 23 adsorption–desorption cycles CMOs also showed a lower CO2 uptake capacity loss (35.7%) than CaO from HPACC (51.3%) and commercial CaCO3 (79.7%). Al was introduced to CMO by the addition of Al(NO3)3 in the synthesis of CMC-3 to give ACMO after calcination. The presence of ∼19 mol% of Al(NO3)3 in ACMO-4 significantly enhanced its stability over 23 cycles (capacity loss of 5.2%) when compared with CMO-3 (calcined CMC-3) without adversely affecting the CO2 uptake. After 100 cycles, ACMO-4 still had a CO2 uptake of 0.219 g g−1. Scanning electron microscope images clearly showed that the presence of Mg and Al in CMO hindered the sintering of CaCO3 at high temperatures and therefore, enhanced the cycle stability of the CMO sorbents. We tested the CO2 uptake properties of CMO and ACMO only under ideal laboratory testing environment, but our results indicated that these materials can be further optimized as good CO2 sorbents for various applications.

A Modified In Situ Method to Determine Release from a Complex Drug Carrier in Particle-Rich Suspensions

Effective and compound-sparing methods to evaluate promising drug delivery systems are a prerequisite for successful selection of formulations in early development stages. The aim of the study was to develop a small-scale in situ method to determine drug release and supersaturation in highly concentrated suspensions of enabling formulations. Mesoporous magnesium carbonate (MMC), which delivers the drug in an amorphous form, was selected as a drug carrier. Five model compounds were loaded into the MMC at a 1:10 ratio using a solvent evaporation technique. The μDiss Profiler was used to study the drug release from MMC in fasted-state simulated intestinal fluid. To avoid extensive light scattering previously seen in particle-rich suspensions in the μDiss Profiler, an in-house-designed protective nylon filter was placed on the in situ UV probes. Three types of release experiments were conducted for each compound: micronized crystalline drug with MMC present, drug-loaded MMC, and drug-loaded MMC with 0.01% w/w hydroxypropyl methyl cellulose. The nylon filters effectively diminished interference with the UV absorption; however, the release profiles obtained were heavily compound dependent. For one of the compounds, changes in the UV spectra were detected during the release from the MMC, and these were consistent with degradation of the compound. To conclude, the addition of protective nylon filters to the probes of the μDiss Profiler is a useful contribution to the method, making evaluations of particle-rich suspensions feasible. The method is a valuable addition to the current ones, allowing for fast and effective evaluation of advanced drug delivery systems.

Amine-functionalised mesoporous magnesium carbonate: Dielectric spectroscopy studies of interactions with water and stability

A mesoporous magnesium carbonate (MMC) material that was first described in 2013 is currently being investigated for several industrial and life-science-based applications. In this paper, the effect of functionalising the surface of MMC with amine groups on the water interaction properties of the material is investigated in detail. Amine functionalisation enhanced the stability and water sorption-release properties of the material. This is explained by the low affinity between amine-functionalised MMC and water molecules, as attested by the high free/total water ratio shown by dielectric spectroscopy. This low affinity had an impact on the total amount of adsorbed water at low relative humidities (RHs) but not at high RHs. The functionalisation of MMC with amine groups also stabilised the material in moist environments, hindering spontaneous crystallisation. These results provide a more fundamental understanding of the water interaction properties of MMC and are also expected to facilitate optimisation of the stability of materials like this for novel drug formulations and other life-science applications, as well as for their use in humidity control.

Enhanced release of poorly water-soluble drugs from synergy between mesoporous magnesium carbonate and polymers

The need to combat poor water solubility has increased interest in supersaturating drug delivery systems. In this study, amorphous mesoporous magnesium carbonate (MMC) was used as a drug carrier to achieve supersaturation of tolfenamic acid and rimonabant, two drug compounds with low aqueous solubility. The potential synergy between MMC and hydroxypropyl methylcellulose (HPMC), a polymer commonly included as a precipitation inhibitor in drug delivery systems, was explored with the aim of extending the time that high supersaturation levels were maintained. Release was studied under physiological conditions using USP-2 dissolution baths. A new small-scale method was developed to enable measurement of the initial drug release occurring when the MMC is immersed in the water phase. It was shown that MMC and HPMC together resulted in significant supersaturation and that the polymer enabled both the achievement of a higher API concentration and extension of the supersaturation period. The new small-scale release method showed that the release was linearly increasing with the dose and that similar release rates were observed for the two model compounds. It was hence concluded that the MMC release was diffusion limited for the compounds explored.

Effects of amine modification of mesoporous magnesium carbonate on controlled drug release

(3-Aminopropyl)triethoxysilane (APTES) was used to modify the surface of mesoporous magnesium carbonate (MMC). The as-synthesized MMC had an average pore diameter of ∼5nm, but amine grafting occurred preferentially on the walls of the largest MMC pores. Analysis of ibuprofen (IBU) loading and release showed that IBU remained stable in the amorphous phase in all the MMC and modified MMC samples. The kinetics of IBU release from the modified MMC were assessed and used to evaluate the effects of the different functional groups. The release rate showed that the release of IBU could be controlled by adjusting the amine surface coverage of MMC and also by changing the surface groups. It was concluded that the interaction between the grafted functional groups in the modified MMC and the OH in the carboxyl groups of IBU was the most important factor for prolonging the release of the drug. These results are expected to lead to investigation of other as yet unexplored applications for MMC, including using it as a plastic additive and for gas separation.

Dynamics of water confined in mesoporous magnesium carbonate.

We have measured the dynamics of water confined in a porous magnesium carbonate material, Upsalite®, using the high-resolution neutron backscattering spectrometer SPHERES. We found quasielastic scattering that does not flatten out up to 360 K, which means that the dynamics of water are much slower than in other matrix materials. Specifically, a single Lorentzian line could be fitted to the quasielastic part of the acquired spectra between 220 and 360 K. This, accompanied by an elastic line from dynamically frozen water present at all experimental temperatures, even above the melting point, signaled a significant amount of bound or slow water.