Mesoporous Carriers Research Articles

The comparison of melt technologies based on mesoporous carriers for improved carvedilol dissolution

High-shear (HS) melt granulation and hot melt extrusion (HME) were compared as perspective melt-based technologies for preparation of amorphous solid dispersions (ASDs). ASDs were prepared using mesoporous carriers (SyloidⓇ 244FP or NeusilinⓇ US2), which were loaded with carvedilol dispersed in polymeric matrix (polyethylene glycol 6000 or SoluplusⓇ). Formulations with high carvedilol content were obtained either by HME (11 extrudates with polymer:carrier ratio 1:1) or HS granulation (6 granulates with polymer:carrier ratio 3:1).DSC and XRD analysis confirmed the absence of crystalline carvedilol for the majority of prepared ADSs, thus confirming the stabilizing effect of selected polymers and carriers over amorphous carvedilol. HME produced larger particles compared to HS melt granulation, which was in line with better flow time and Carr index of extrudates. Moreover, SEM images revealed smoother surface of ASDs obtained by HME, contributing to less obstructed flow. The rougher and more porous surface of HS granules was correlated to larger granule specific surface area, manifesting in faster carvedilol release from SyloidⓇ 244FP-based granules, as compared to their HME counterparts. Regarding dissolution, the two HS-formulations performed superior to pure crystalline carvedilol, thereby confirming the suitability of HS melt granulation for developing dosage forms with improved carvedilol dissolution.

QbD-based formulation development of resveratrol nanocrystal incorporated into soluble mesoporous material: Pharmacokinetic proof of concept study

Resveratrol (RSV) has powerful antioxidant activities. However, the bioavailability is still limited due to low solubility and transport issues. Nanocrystal technology has been introduced to address these issues; however, the bulky formulation of the nanocrystal process through nanosuspension faces a big challenge in terms of stability and scale-up ability. This work aimed to enhance the bioavailability of RSV through nanocrystal formulation incorporated into soluble mesoporous carriers for superior solid-state stability and feasibility. This formulation was designed and developed rationally through scientific justification in the nanocrystal formulation along with quality by design paradigm. Box-Behnken design was applied to determine the optimized formulation based on the particle size and distribution, drug loading, zeta potential, and supersaturation parameters. The nanocrystal was formed through evaporation of drug, polymer, and surfactant in the solvent incorporated into mesoporous material. The nanocrystal was evaluated by vibrational spectroscopy, thermal analyses, and SEM and TEM photographs, followed by crystallinity evaluation. The results indicated that the factors only affected the particle size variation, zeta potential, drug loading, and the time to reach the supersaturation peak level. The optimized formulation was achieved by 68 % desirability value, producing 133.3 ± 1.2 nm particle size and −24.6 mV zeta potential. The physical and chemical evaluation characterization indicated no interaction between RSV and carrier. In addition, there was no difference in crystallinity between the RSV nanocrystal and native RSV. Moreover, the RSV nanocrystal improved the bioavailability nearly twice compared to the RSV suspension.

Evaluation of Suitable Polymeric Matrix/Carriers during Loading of Poorly Water Soluble Drugs onto Mesoporous Silica: Physical Stability and In Vitro Supersaturation.

The application of mesoporous carriers in formulations of amorphous solid dispersions (ASDs) has been suggested to enhance the stability of amorphous drugs. However, mesoporous carriers do not demonstrate satisfactory inhibitory effects on the precipitation of active pharmaceutical ingredients (APIs), and the inclusion of an appropriate polymer within ASDs becomes imperative to maintaining drug supersaturation. The aim of this study was to evaluate ternary olanzapine (OLN) ASDs with Syloid 244FP and to find an appropriate polymeric carrier. The polymer's selection criteria were based on the physical stability of the ASDs and the release rate of the drug from the systems. The polymers investigated were hydroxypropylmethyl cellulose (HPMC) and copovidone (coPVP). The formation of ASDs was achievable in all investigated cases, as demonstrated by the complete lack of crystallinity confirmed through both powder X-ray diffraction (pXRD) analysis and differential scanning calorimetry (DSC) for all developed formulations. The solvent shift method was employed to evaluate the ability of the studied carriers to inhibit the precipitation of supersaturated OLN. coPVP emerged as a more suitable precipitation inhibitor compared with HPMC and Syloid 244 FP. Subsequently, in vitro dissolution studies under non-sink conditions revealed a higher degree of supersaturation in ternary systems where coPVP was used as a polymeric carrier, as these systems exhibited, under the examined conditions, up to a 2-fold increase in the released OLN compared with the pure crystalline drug. Moreover, stability studies conducted utilizing pXRD demonstrated that ternary formulations incorporating coPVP and Syloid 244 FP maintained stability for an extended period of 8 months. In contrast, binary systems exhibited a comparatively shorter stability duration, indicating the synergistic effect of coPVP and Syloid 244 FP on the physical stability of the amorphous API. Attenuated total reflectance-Fourier transform infrared (ATR-FTIR) studies showed that the development of stronger molecular interactions can be provided as an explanation for this synergistic effect, as the formation of robust H-bonds may be considered responsible for inhibiting the precipitation of the supersaturated API. Therefore, the incorporation of coPVP into OLN ASDs with Syloid 244 FP is considered a highly promising technique for increasing the degree of OLN supersaturation in in vitro dissolution studies and improving the stability of systems.

Polyamine functionalized cage hollow mesoporous SiO2 microspheres for CO2 capture over a wide temperature range

Hollow SiO2 microspheres have become attractive materials for nanotechnology applications owing to their biological inertness and high functionality. In this study, hydrophobic spherical hollow cages were formed using the soft stencil method with Pluronic F127 and cetyltrimethylammonium bromide (CTAB) as the structure-directing agent, and hollow nanoporous SiO2 microspheres (FHMS) were prepared using the soft template method. Various of amine functionalization modes were further employed to demonstrate the complexity of the relationship between pore structure/amidation mode/amine content and adsorption capacity. The hollow morphology of the porous silica was revealed using field-emission scanning electron microscopy (SEM) and transmission electron microscopy (TEM), and its porous properties were revealed using nitrogen adsorption-desorption isotherm measurements. Experiments on the fixed-bed dynamic adsorption process at 15% CO2 showed that the high specific surface area, high pore volume and amine content of the carriers had a positive effect on the adsorption performance. However, the accessibility of the adsorption centre was affected at high loadings, and the amine efficiency and adsorption capacity were reduced. The dual amine functionalized FHMS-G-I60 maintained the integrity and order of the hollow mesoporous carrier structure, and overcame the dilemma of easy loss in the cycle process of the impregnation method and the low adsorption capacity of the grafting method. It possessed an adsorption capacity of 3.62 mmol/g, high adsorption cycling stability (more than 99.5% adsorption maintained after 10 cycles) and high amine efficiency (0.2852 mmol CO2/mmol N). CO2-TPD analysis (Thermal Programmed Desorption) further showed that FHMS-G-I60 had a faster desorption rate and lower regeneration energy consumption. In general, such structure-directed prepared matrices and functionalized with different amines are promising and low-cost adsorbents that can be used to capture CO2 from ambient air and flue gases under different demands.

High loading of lipophilic compounds in mesoporous silica for improved solubility and dissolution performance

Loading poorly soluble active pharmaceutical ingredients (API) into mesoporous silica can enable API stabilization in non-crystalline form, which leads to improved dissolution. This is particularly beneficial for highly lipophilic APIs (log D7.4 > 8) as these drugs often exhibit limited solubility in dispersion forming carrier polymers, resulting in low drug load and reduced solid state stability. To overcome this challenge, we loaded the highly lipophilic natural products coenzyme Q10 (CoQ10) and astaxanthin (ASX), as well as the synthetic APIs probucol (PB) and lumefantrine (LU) into the mesoporous silica carriers Syloid® XDP 3050 and Silsol® 6035. All formulations were physically stable in their non-crystalline form and drug loads of up to 50 % were achieved. At increasing drug loads, a marked increase in equilibrium solubility of the active ingredients in biorelevant medium was detected, leading to improved performance during biorelevant biphasic dissolution studies (BiPHa + ). Particularly the natural products CoQ10 and ASX showed substantial benefits from being loaded into mesoporous carrier particles and clearly outperformed currently available commercial formulations. Performance differences between the model compounds could be explained by in silico calculations of the mixing enthalpy for drug and silica in combination with an experimental chromatographic method to estimate molecular interactions.

Preparation of surface molecular imprinting fluorescent sensor based on magnetic porous silica for sensitive and selective determination of catechol.

A magnetic fluorescent molecularly imprinted sensor was successfully prepared and implemented to determine catechol (CT). Fe3O4 nanoparticles were synthesized by the solvothermal technique and mesoporous Fe3O4@SiO2@mSiO2 imprinted carriers were prepared by coating nonporous and mesoporous SiO2 shells on the surface of the Fe3O4 subsequently. The magnetic surface molecularly imprinted fluorescent sensor was created after the magnetic mesoporous carriers were modified with γ-methacryloxyl propyl trimethoxy silane to introduce double bonds on thesurface of the carries and the polymerization was carried out in the presence of CT and fluorescent monomers. The magnetic mesoporous carriers were modified with γ-methacryloxyl propyl trimethoxy silane and double bonds were introduced on the surface of the carriers. After CT binding with the molecularly imprinted polymers (MIPs), the fluorescent intensity of the molecularly imprinted polymers (Ex = 400nm, Em = 523nm) increased significantly. The fluorescent intensity ratio (F/F0) of the sensor demonstrated a favorable linear correlation with the concentration of CT between 5 and 50μM with a detection limit of 0.025μM. Furthermore, the sensor was successfully applied to determine CT in actual samples with recoveries of 96.4-105% and relative standard deviations were lower than 3.5%. The results indicated that the research of our present work provided an efficient approach for swiftly and accurately determining organic pollutant in water.

Effect of Additives on CO2 Adsorption of Polyethylene Polyamine-Loaded MCM-41.

Organic amine-modified mesoporous carriers are considered potential CO2 sorbents, in which the CO2 adsorption performance was limited by the agglomeration and volatility of liquid amines. In this study, four additives of ether compounds were separately coimpregnated with polyethylene polyamine (PEPA) into MCM-41 to prepare the composite chemisorbents for CO2 adsorption. The textural pore properties, surface functional groups and elemental contents of N for MCM-41 before and after functionalization were characterized; the effects of the type and amount of additives, adsorption temperature and influent velocity on CO2 adsorption were investigated; the amine efficiency was calculated; and the adsorption kinetics and regeneration for the optimized sorbent were studied. For 40 wt.% PEPA-loaded MCM-41, the CO2 adsorption capacity and amine efficiency at 60 °C were 1.34 mmol/g and 0.18 mol CO2/mol N, when the influent velocity of the simulated flue gas was 30 mL/min, which reached 1.81 mmol/g and 0.23 mol CO2/mol N after coimpregnating 10 wt.% of 2-propoxyethanol (1E). The maximum adsorption capacity of 2.16 mmol/g appeared when the influent velocity of the simulated flue gas was 20 mL/min. In addition, the additive of 1E improved the regeneration and kinetics of PEPA-loaded MCM-41, and the CO2 adsorption process showed multiple adsorption routes.

Comparison of the liquisolid technique and co-milling for loading of a poorly soluble drug in inorganic porous excipients

Drug loading into mesoporous carriers may help to improve the dissolution of poorly aqueous-soluble drugs. However, both preparation method and carrier properties influence loading efficiency and drug release. Accordingly, this study aimed to compare two preparation methods: formulation into liquisolid systems (LSS) and co-milling for their efficiency in loading the poorly soluble model drug cyclosporine A (CyA) into mesoporous magnesium aluminometasilicate Neusilin® US2 (NEU) or functionalized calcium carbonate (FCC). Scanning electron microscopy was used to visualize the morphology of the samples and evaluate the changes that occurred during the drug loading process. The solid-state characteristics and physical stability of the formulations, prepared at different drug concentrations, were determined using X-ray powder diffraction. In vitro release of the drug was evaluated in biorelevant media simulating intestinal fluid. The obtained results revealed improved drug release profiles of the formulations when compared to the milled (amorphous) CyA alone. The dissolution of CyA from LSS was faster in comparison to the co-milled formulations. Higher drug release was achieved from NEU than FCC formulations presumably due to the higher pore volume and larger surface area of NEU.

Rational Design and Development of a Soluble Mesoporous Carrier for the Solidification of a Preconcentrated Self-Nanoemulsion Formulation.

The solidification of self-preconcentrated nanoemulsion without changes in nanodroplet formation gains particular consideration due to the interaction between solidified carriers. This work aimed to develop mannitol mesoporous as a soluble carrier for supersaturated self-nanoemulsion (SSNE) using a design of experiment (DoE) approach. The mesoporous carrier was prepared by a spray-drying technique. The type of templating agent (TA) used to form a porous system, the amount of TA, and solid loading in the spray-drying process were studied. Several characterizations were performed for mannitol mesoporous formation, namely, powder X-ray diffraction, thermal analysis, scanning electron microscopy, and surface area analyzer. Solidification of SSNE incorporated into the mesoporous mannitol was carried out, followed by compaction behavior, flowability, and nanodroplet formation. The results revealed several process parameters for preparing the mesoporous mannitol, notably TA, which gained more significant consideration. Solid loading in the mesoporous preparation system reduced the surface area and pore size and did not affect solid SSNE flowability. The amount of TA increased the pore size and volume dramatically as well as the compactibility and flowability. Ammonium carbonate was the preferable TA for preparing the mesoporous carrier, particularly for the nanodroplet formulation process. In addition, synergistic and antagonistic interactions between factors were also observed. The optimized mesoporous carrier was applied for solidification, and there was no difference between SSNE and solid SSNE in the performance of nanodroplet formation.

Enabling direct compression tablet formulation of celecoxib by simultaneously eliminating punch sticking, improving manufacturability, and enhancing dissolution through co-processing with a mesoporous carrier

The development of a high quality tablet of Celecoxib (CEL) is challenged by poor dissolution, poor flowability, and high punch sticking propensity of CEL. In this work, we demonstrate a particle engineering approach, by loading a solution of CEL in an organic solvent into a mesoporous carrier to form a coprocessed composite, to enable the development of tablet formulations up to 40% (w/w) of CEL loading with excellent flowability and tabletability, negligible punch sticking propensity, and a 3-fold increase in in vitro dissolution compared to a standard formulation of crystalline CEL. CEL is amorphous in the drug-carrier composite and remained physically stable after 6 months under accelerated stability conditions when the CEL loading in the composite was ≤ 20% (w/w). However, crystallization of CEL to different extents from the composites was observed under the same stability condition when CEL loading was 30–50% (w/w). The success with CEL encourages broader exploration of this particle engineering approach in enabling direct compression tablet formulations for other challenging active pharmaceutical ingredients.

Effect of amorphous ordered mesoporous carrier on adsorption and desorption of Hg0 over CeOx-amTiO2

Improper disposal of deactivated mercury (Hg) adsorbents will cause secondary contamination which is still hazardous to human beings. Wet desorption is a green and environmentally friendly method, but there is a lack of sufficient study. In this work, a cerium oxide loaded ordered mesoporous amorphous titanium dioxide (CeOx-amTiO2) composite is obtained based on the evaporation-induced self-assembly (EISA) process. It possesses a high specific surface area (∼198 m2/g), uniform pore diameters (∼14.7 nm), and large pore volume (∼0.49 cm3/g). The CeOx-amTiO2 demonstrates high adsorption capacity in various atmospheres (63.3 % in pure N2, 95.0 % in N2 + 400 ppm H2S), and achieves a desorption efficiency of 93.2 % in 0.2 mol/L sodium thiosulfate (Na2S2O3) solution. The large specific surface area and ordered mesostructure significantly facilitate the mass transfer process, reasonably explaining the strong adsorption capacity and fast desorption kinetics. X-ray photoelectron spectroscopy (XPS) characterization and thermodynamic calculations reveal that the reduction of Ce3+ plays a key role in the desorption of Hg. In addition, the amorphous carrier structure reduces the binding strength between the adsorption product and the adsorbent, further accelerating the desorption process. This study provides a pathway for the efficient desorption of Hg0 removal adsorbents.

In vitro Antitumor Properties of Fucoidan-Coated, Doxorubicin-Loaded, Mesoporous Polydopamine Nanoparticles

Chemotherapy is a common method for tumor treatment. However, the non-specific distribution of chemotherapeutic drugs causes the death of normal cells. Nanocarriers, particularly mesoporous carriers, can be modified to achieve targeted and controlled drug release. In this study, mesoporous polydopamine (MPDA) was used as a carrier for the antitumor drug doxorubicin (DOX). To enhance the release efficiency of DOX in the tumor microenvironment, which contains high concentrations of glutathione (GSH), we used N,N-bis(acryloyl)cysteamine as a cross-linking agent to encapsulate the surface of MPDA with fucoidan (FU), producing MPDA-DOX@FU-SS. MPDA-DOX@FU-SS was characterized via transmission electron microscopy, thermogravimetric analysis, and X-ray photoelectron spectroscopy (XPS), and its antitumor efficacy in vitro was investigated. The optimal conditions for the preparation of MPDA were identified as pH 12 and 20 °C, and the optimal MPDA-to-FU ratio was 2:1. The DOX release rate reached 47.77% in an in vitro solution containing 10 mM GSH at pH 5.2. When combined with photothermal therapy, MPDA-DOX@FU-SS significantly inhibited the growth of HCT-116 cells. In conclusion, MPDA-DOX@FU-SS may serve as a novel, highly effective tumor suppressor that can achieve targeted drug release in the tumor microenvironment.

Magnetic Porous Silica-lipid Bilayer Hybrid Carriers for Target Delivery of Curcumin

Mesoporous silica nanoparticles with embedded magnetic particles and sizes around 80 nm were prepared. Curcumin loading in mesoporous silica was realized by a post-synthesis impregnation procedure. The loaded particles were additionally modified by surface coating with a phospholipid bilayer of a thickness of around 5 nm changing the surface charge of the carrier from negative to positive, which enables the efficient attachment to cells, increasing the probability of cellular uptake. The non-loaded, curcumin loaded and their surface-coated counterparts were characterized by XRD, N2 physisorption, thermal analysis, TEM, and ATR-FTIR spectroscopy. Release experiments were performed and demonstrated that the phospholipid coating contributed greatly a sustained drug release to be achieved. A comparative study on the antiproliferative effect of curcumin loaded into the mesoporous carrier and lipid-coated vs. free drug was performed on a panel of three human cell lines. On the basis of the obtained results, it can be concluded that obtained hybrid magnetic silica-lipid particles are promising carriers of curcumin.

Immobilization of Metronidazole on Mesoporous Silica Materials

Metronidazole (MTZ) is a widely used drug, but due to its many side effects, there is a growing trend today to use a minimum dose while maintaining high efficacy. One way to meet this demand is to reduce the size of the drug particles. A relatively new method of size reduction is attaching the drug molecules to a mesoporous carrier. In this paper, we studied the fixation of MTZ molecules on mesoporous silica carriers. The drug was immobilized on two mesoporous silica materials (Syloid, SBA-15) with the use of a variety of immersion techniques and solvents. The immobilized drug was subjected to physicochemical examinations (e.g., SEM, XPS, XRD, nitrogen uptake, DSC) and dissolution studies. A significantly higher immobilization was attained on SBA-15 than on a Syloid carrier. Among the processing parameters, the type of MTZ solvent had the highest influence on immobilization. Ultrasonic agitation had a lower but still significant impact, while the concentration of MTZ in the solution made no difference. Under optimal conditions, with the application of an ethyl acetate solution, the surface coverage on SBA-15 reached as much as 91%. The immobilized MTZ exhibited a ca. 10% faster dissolution rate as compared to the pure micron-sized drug particles.

High-Shear Wet Granulation of SMEDDS Based on Mesoporous Carriers for Improved Carvedilol Solubility.

Mesoporous carriers are a convenient choice for the solidification of self-microemulsifying drug delivery systems (SMEDDS) designed to improve the solubility of poorly water-soluble drugs. They are known for high liquid load capacity and the ability to maintain characteristics of dry, free-flowing powders. Therefore, five different mesoporous carriers were used for the preparation of carvedilol-loaded SMEDDS granules by wet granulation methods—in paten (manually) and using a high-shear (HS) granulator. Granules with the highest SMEDDS content (63% and 66% of total granules mass, respectively) and suitable flow properties were obtained by Syloid® 244FP and Neusilin® US2. SMEDDS loaded granules produced by HS granulation showed superior flow characteristics compared to those obtained manually. All SMEDDS granules exhibited fast in vitro release, with 93% of carvedilol releasing from Syloid® 244FP-based granules in 5 min. Upon compaction into self-microemulsifying tablets, suitable tablet hardness and very fast disintegration time were achieved, thus producing orodispersible tablets. The compaction slightly slowed down the carvedilol release rate; nevertheless, upon 1 h (at pH 1.2) or 4 h (at pH 6.8) of in vitro dissolution testing, the amount of released drug was comparable with granules, confirming the suitability of orodispersible tablets for the production of the SMEDDS loaded single unit oral dosage form.

Development of nanohybrid dental composite containing mesoporous carrier silica particles: Synthesis particles, determination of fluoride adsorption capacities, and addition of the composite

AbstractMesoporous, nanometric silica particles that can serve both as carrier and filler for fluoride were synthesized, and their release properties were later investigated. The flexural and compressive strengths performances of organic matrix and composite materials were evaluated using the tests defined in BS EN ISO 4049. From the Brunauer–Emmett–Teller results of the synthesized mesoporous silica particles, mesoporous SiO2 particles‐6 (MSP‐6) was preferred because it fits the MSP‐6 Type V isotherm model and has a highly mesoporous structure. The saturation points of MSP‐6 and R709 silica particles in terms of fluoride were determined as 180 min for MSP‐6 and 120 min for R709, respectively. The strength of composites prepared after the treatment of surface‐modified R709 silica particles with fluoride solution decreased, an increase was observed in the composites prepared after MSP‐6 particles were treated with fluoride solution. The porous silica particles caused a slight increase in the compressive strength of the composites. The standard deviations of the compression values of the fluorine‐containing composites F/R709 and F/MSP‐6 are quite low. The microhardness values of R709, F/R709, MSP6 and F/MSP6 samples were determined as 82.1 ± 8.59, 247.67 ± 12.32, 131.03 ± 10.98, and 218.8 ± 11.24, respectively. Especially considering the effect of chewing force the surface hardness of the composite is also directly related to the compressive strength. The increase in the compressive strength of the samples treated with fluoride confirms this result. A high rate of mesoporous structure silica particles was synthesized and could serve both as a carrier for fluoride and as a filler required by the material.

Curcumin and Capsaicin-Loaded Ag-Modified Mesoporous Silica Carriers: A New Alternative in Skin Treatment.

Biologically active substances of natural origin offer a promising alternative in skin disease treatment in comparison to synthetic medications. The limiting factors for the efficient application of natural compounds, such as low water solubility and low bioavailability, can be easily overcome by the development of suitable delivery systems. In this study, the exchange with the template procedure was used for the preparation ofa spherical silver-modified mesoporous silica nanocarrier. The initial and drug-loaded formulations are fully characterized by different physico-chemical methods. The incipient wetness impregnation method used to load health-promoting agents, curcumin, and capsaicin in Ag-modified carriers separately or in combinationresulted in high loading efficiency (up to 33 wt.%). The interaction between drugs and carriers was studied by ATR-FTIR spectroscopy. The release experiments of both active substances from the developed formulations were studied in buffers with pH 5.5, and showed improved solubility. Radical scavenging activity and ferric-reducing antioxidant power assays were successfully used for the evaluation of the antiradical and antioxidant capacity of the curcumin or/and capsaicin loaded on mesoporous carriers. Formulations containing a mixture of curcumin and capsaicin were characterized bypotentiation of their antiproliferative effect against maligning cells, and it was confirmed that the system for simultaneous delivery of both drugs has lower IC50 values than the free substances.The antibacterial tests showed better activity of the obtained delivery systems in comparison with the pure curcumin and capsaicin. Considering the obtained results, it can be concluded that the obtained delivery systems are promising for potential dermal treatment.

Study of the Technological Methods Effect on Dissolution of the X-ray Amorphous Efavirenz-mesoporous Carrier System

Introduction. The low solubility of active pharmaceutical ingredients (APIs) in the physiological pH range of the intestinal tract can adversely affect their absorption and bioavailability. Various methods of increasing the solubility of APIs have been proposed in recent decades. Among them there are preparation of solid dispersions, micronization, solubilization and other methods, including ones based on the amorphization of the crystalline substances, such as, spray drying, hot melt extrusion, absorption on mesoporous carriers such as magnesium aluminosilicate, silica, etc.Aim. Study the technological methods effect on dissolution at physiological temperature and pH range of practically insoluble API efavirenz amorphized by absorption on mesoporous carriers.Materials and methods. Efavirenz form І (EFA) (LLC "AMEDART", Russia, batch 010520). Efavirenz reference standard (USP № R09740). Mesoporous carriers (MC): Silica – Syloid® 244FP (244), Syloid® XDP 3150 (3150) (W.R. Grace&Co.-Conn, USA); FujiSil™ (FSL) (Fuji Chemical Industries Co., Ltd., Japan); Aeroperl® 300 (APL) (Evonik, Germany); Parteck® SLC (SLC) (Merck Millipore, USA); Synthetic magnesium aluminometasilicate – Neusilin® US2 (US2), Neusilin® UFL (UFL) (Fuji Chemical Industry Co., Ltd., Japan). The API absorption on MC was performed via solvent wetting and hot melt extrusion methods.Results and discussion. The dissolution increases in the MC series as the following: SLC > FSL > UFL = US2 > 244 = 3150. The data are consistent with an increase in the surface area and a decrease in the pore size of MC. The crystalline state of the system API efavirenz-Aeroperl® is caused by the largest pore size. It is obvious according to the data that the solvent wetting method gives better results in comparison with the hot melt extrusion as the method of obtaining X-ray amorphous systems API efavirenz-MC.Conclusion. Solvent wetting technology is recommended for increasing the dissolution of practically insoluble APIs. The preferable mesoporous carriers are silica Parteck® SLC or synthetic magnesium aluminometasilicate Neusilin® US2.

Complex dispersions of poloxamers and mesoporous carriers with ibrutinib

Ibrutinib is an anticancer drug, a Bruton's tyrosine kinase inhibitor with poor solubility in aqueous media. This study reports on the study of the effectiveness of mesoporous carriers based on magnesium aluminometasilicate and poloxamers to improve the solubility and bioavailability of ibrutinib in the form of amorphous solid dispersions. The choice of the most effective composition was made on a parallel study of (a) a physical mixture of ibrutinib with a mesoporous carrier, (b) a solid dispersion with a poloxamer on a non-porous carrier, (c) a dispersion with a poloxamer deposited on a mesoporous carrier. Sample mixtures and dispersions with ibrutinib were tested to establish amorphism by various methods and to determine the solubility in aqueous media. The composition of ibrutinib-poloxamer P407-mesoporous carrier showed the best results in three standard media regarding the solubility of ibrutinib (increase in solubility at pH 1.2 - 129.6%, pH 4.5 - 300.2%, pH 6.8 - 363.3%). This composition became the basis for the tablet formulation and showed the best results in the Dissolution test (the dosage was dissolved in only 10 min of the test in pH 1.2 medium by 98.3%, pH 4.5 - 95.4%, pH 6.8 – 57.3%). These results were superior to those of the original Imbruvica capsules at all points in the study. In conclusion, the resulting formulation was stable under accelerated conditions according to the ICH Q1 Quality Guideline (40 °C, 75% relative humidity, 6 months).

Comparative Study of Methods for the Pharmaceutical Preparation and Effectiveness of Darunavir Ethanolate Compositions with Mesoporous Carriers and Polymer Solid Dispersions

Comparative Study of Methods for the Pharmaceutical Preparation and Effectiveness of Darunavir Ethanolate Compositions with Mesoporous Carriers and Polymer Solid Dispersions