In the pharmaceutical industry, silicates are commonly used excipients with different application possibilities. They are especially utilized as glidants in low concentrations, but they can be used in high concentrations as porous carriers and coating materials in oral solid drug delivery systems. The desirable formulations of such systems must exhibit good powder flow but also good compactibility, which brings opposing requirements on inter-particle interactions. Since magnesium aluminometasilicates (MAS) are known for their interesting flow behavior reported as "negative cohesivity" yet they can be used as binders for tablet compression, the objective of this experimental study was to investigate their particle interactions within a broad range of mechanical stress from several kPa to hundreds of MPa. Magnesium aluminometasilicate (Neusilin® US2 and Neusilin® S2)-microcrystalline cellulose (Avicel® PH102) physical powder mixtures with varying silicate concentrations were prepared and examined during their exposure to different pressures using powder rheology and compaction analysis. The results revealed that MAS particles retain their repulsive character and small contact surface area under normal conditions. If threshold pressure is applied, the destruction of MAS particles and formation of new surfaces leading to particle interactions are observed. The ability of MAS particles to form interactions intensifies with increasing pressure and their amount in a mixture. This "function switching" makes MAS suitable for use as multifunctional excipients since they can act as a glidant or a binder depending on the applied pressure.

• Klíčová slova
• formulation development, glidant, magnesium aluminometasilicates, particle interactions, threshold behavior,
• Publikační typ
• časopisecké články MeSH

Albeit the preparation of liquisolid systems represents an innovative approach to enhance the dissolution of poorly soluble drugs, their broader utilization is still limited mainly due to the problematic conversion of the liquid into freely flowing and readily compressible powder. Accordingly, the presented study aims to determine the optimal carrier/coating material ratio (R value) for formulations based on magnesium aluminometasilicate (NUS2) loaded with polyethylene glycol 400. Four commercially available colloidal silica were used as coating materials in nine different R values (range of 5 - 100). The obtained results suggested that the higher R value leads to the superior properties of powder mixtures, such as better flowability, as well as compacts with higher tensile strength and lower friability. Moreover, it was observed that the type of coating material impacts the properties of liquisolid systems due to the different arrangement of particles in the liquisolid mixture. To confirm the noted dependency of R value and coating material type, the one- and two-way ANOVA, linear regression and principal component analysis (PCA) techniques were performed. In addition, a comparison of results with the properties of loaded NUS2 itself revealed that LSS with sufficient properties may be prepared even without the coating material.

• Klíčová slova
• Carrier/coating material ratio, Colloidal silica, Liquisolid systems, Mesoporous silica, Neusilin® US2,
• MeSH
• hořčík * MeSH
• oxid křemičitý * MeSH
• prášky, zásypy, pudry MeSH
• příprava léků MeSH
• rozpustnost MeSH
• tablety MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• hořčík * MeSH
• oxid křemičitý * MeSH
• prášky, zásypy, pudry MeSH
• tablety MeSH

A method of preparing tablets called liquisolid technique is currently emerging. In these formulations, an important role is played by porous carriers, which are the basic building blocks of liquisolid systems (LSSs). The most common are microcrystalline cellulose (MCC), magnesium aluminometasilicates, silica aerogels, mesoporous silicates, clays, etc. In this study, magnesium aluminometasilicate is used to prepare modified LSS formulations with plant extracts as model drugs dissolved in water (W) or ethanol (E). The modification involves drying tablets in a microwave (MW) and hot air dryer (HA) for a specified period. Powder blends and tablets were evaluated for physical properties, and their antioxidant activity (AA) was measured in a modified dissolution by ferric reducing antioxidant power assay (FRAP). PLS and ANOVA were used to compare tablets properties depending on the composition and technology. The experiment is based on a previous one, in which the plant extracts were processed into tablets using a similar method. Therefore, extending the study to include more plants and the robust statistical evaluation and comparison of the products was a procedure to justify the suitability of the presented method for a wide range of liquid plant extracts. As a result, we obtained tablets with excellent physical properties, including a short disintegration and dissolution, which is problematic in tableted extracts.

• Klíčová slova
• adsorption, antioxidant activity, liquisolid systems, magnesium aluminometasilicates, plant extracts, porous carriers,
• Publikační typ
• časopisecké články MeSH

Burst drug release is often considered a negative phenomenon resulting in unexpected toxicity or tissue irritation. Optimal release of a highly soluble active pharmaceutical ingredient (API) from hypromellose (HPMC) matrices is technologically impossible; therefore, a combination of polymers is required for burst effect reduction. Promising variant could be seen in combination of HPMC and insoluble Eudragits® as water dispersions. These can be applied only on API/insoluble filler mixture as over-wetting prevention. The main hurdle is a limited water absorption capacity (WAC) of filler. Therefore, the object of this study was to investigate the dissolution behavior of levetiracetam from HPMC/Eudragit®NE matrices using magnesium aluminometasilicate (Neusilin® US2) as filler with excellent WAC. Part of this study was also to assess influence of thermal treatment on quality parameters of matrices. The use of Neusilin® allowed the application of Eudragit® dispersion to API/Neusilin® mixture in one step during high-shear wet granulation. HPMC was added extragranularly. Obtained matrices were investigated for qualitative characteristics, NMR solid-state spectroscopy (ssNMR), gel layer dynamic parameters, SEM, and principal component analysis (PCA). Decrease in burst effect (max. of 33.6%) and dissolution rate, increase in fitting to zero-order kinetics, and paradoxical reduction in gel layer thickness were observed with rising Eudragit® NE concentration. The explanation was done by ssNMR, which clearly showed a significant reduction of the API particle size (150-500 nm) in granules as effect of surfactant present in dispersion in dependence on Eudragit®NE amount. This change in API particle size resulted in a significantly larger interface between these two entities. Based on ANOVA and PCA, thermal treatment was not revealed as a useful procedure for this system.

• Klíčová slova
• Burst effect, Eudragit® NE30D, HPMC, Levetiracetam, Neusilin® US2, gel layer, matrix tablets, multivariate data analysis, thermal treatment,
• MeSH
• aplikace orální MeSH
• gely MeSH
• kyseliny polymethakrylové aplikace a dávkování   chemie   metabolismus   MeSH
• léky s prodlouženým účinkem aplikace a dávkování   chemie   metabolismus   MeSH
• magnetická rezonanční spektroskopie metody   MeSH
• pomocné látky chemie   MeSH
• rozpustnost MeSH
• silikáty aplikace a dávkování   chemie   metabolismus   MeSH
• sloučeniny hliníku aplikace a dávkování   chemie   metabolismus   MeSH
• sloučeniny hořčíku aplikace a dávkování   chemie   metabolismus   MeSH
• uvolňování léčiv MeSH
• velikost částic MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• aluminum magnesium silicate MeSH Prohlížeč
• gely MeSH
• kyseliny polymethakrylové MeSH
• léky s prodlouženým účinkem MeSH
• methylmethacrylate-methacrylic acid copolymer MeSH Prohlížeč
• pomocné látky MeSH
• silikáty MeSH
• sloučeniny hliníku MeSH
• sloučeniny hořčíku MeSH

High specific surface area (SSA), porous structure, and suitable technological characteristics (flow, compressibility) predetermine powder carriers to be used in pharmaceutical technology, especially in the formulation of liquisolid systems (LSS) and solid self-emulsifying delivery systems (s-SEDDS). Besides widely used microcrystalline cellulose, other promising materials include magnesium aluminometasilicates, mesoporous silicates, and silica aerogels. Clay minerals with laminar or fibrous internal structures also provide suitable properties for liquid drug incorporation. This work aimed at a comparison of 14 carriers' main properties. Cellulose derivatives, silica, silicates, and clay minerals were evaluated for flow properties, shear cell experiments, SSA, hygroscopicity, pH, particle size, and SEM. The most promising materials were magnesium aluminometasilicates, specifically Neusilin® US2, due to its proper flow, large SSA, etc. Innovative materials such as FujiSil® or Syloid® XDP 3050 were for their properties evaluated as suitable. The obtained data can help choose a suitable carrier for formulations where the liquid phase is incorporated into the solid dosage form. All measurements were conducted by the same methodology and under the same conditions, allowing a seamless comparison of property evaluation between carriers, for which available company or scientific sources do not qualify due to different measurements, conditions, instrumentation, etc.

• Klíčová slova
• adsorption, aluminometasilicates, liquisolid systems, pharmaceutical technology, powder carriers, solid dosage form,
• Publikační typ
• časopisecké články MeSH

Pellets with an immobilized enzyme (acetyl- or butyrylcholinesterase) are the up-to-date type of carriers used for the detection of nerve agents (soman, sarin, tabun, VX, Novichok) and other cholinesterase inhibitors such as organophosphate and carbamate insecticides (parathion, malathion). They are used in the glass detection tubes as a layer containing the enzyme together with the second layer, which contains a colorimetric reagent and substrate. The detection method is based on the visually or spectrophotometrically observable Ellman's reaction, which develops a yellow color in the absence of the cholinesterase inhibitor; otherwise, the detector preserves its original color (preferably white). This reaction occurs very fast and has a high sensitivity to nerve agents but it suffers from an indistinctive color transition from white to yellow. In the presented study, a new approach with the use of the synergic effect of magnesium aluminometasilicate with a high surface area marketed as Neusilin®US2 and a protective semipermeable Eudragit® RL layer was utilized. The prepared pellets have been evaluated for their properties such as the activity of the enzyme, intensity of the developed yellow color, sensitivity to cholinesterase inhibitor physostigmine, which acts as a nerve agent simulant, and physical parameters such as hardness, pycnometric density and sphericity. After the initial evaluation, all samples underwent a stability test under three different storage conditions for 24 months during which they were evaluated at given time points (0, 3, 6, 12 and 24 months). It was found that the prepared samples achieved a much higher intensity of developed yellow color than in the published studies while maintaining similar or better sensitivity, speed of detection and suitable physico-chemical properties.

• Klíčová slova
• Cholinesterase, Color transition, Detection tube, Nerve agent, Neusilin, Stability,
• MeSH
• acetylcholinesterasa chemie   MeSH
• butyrylcholinesterasa chemie   MeSH
• časové faktory MeSH
• cholinesterasové inhibitory analýza   MeSH
• enzymy imobilizované chemie   MeSH
• kolorimetrie metody   MeSH
• nervová bojová látka analýza   MeSH
• polymery chemie   MeSH
• silikáty chemie   MeSH
• sloučeniny hliníku chemie   MeSH
• sloučeniny hořčíku chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• acetylcholinesterasa MeSH
• aluminum magnesium silicate MeSH Prohlížeč
• butyrylcholinesterasa MeSH
• cholinesterasové inhibitory MeSH
• enzymy imobilizované MeSH
• Eudragit RL MeSH Prohlížeč
• nervová bojová látka MeSH
• polymery MeSH
• silikáty MeSH
• sloučeniny hliníku MeSH
• sloučeniny hořčíku MeSH

The aim of the presented research was the preparation of an innovative carrier with significantly improved properties for the fast and sensitive detection of cholinesterase inhibitors such as nerve agents. This innovative carrier was in the form of spherical pellets containing different amounts of Neusilin. Neusilin is a synthetic and amorphous form of magnesium aluminometasilicate with a high specific surface area, and the immobilized enzyme butyrylcholinesterase with an activity of 50nkat·g-1. Pellets were prepared by the extrusion-spheronization method and dried in a hot air oven under two conditions - at 30°C for 72h and at 60°C for 24h. Dried pellets were consequently impregnated with a solution containing butyrylcholinesterase. Impregnated pellets were evaluated for their quality parameters, enzymatic activity and inhibition. Activity and inhibition were tested according to the standard Ellman's method. It was observed that the addition of Neusilin significantly increased the hardness, intraparticular porosity, sphericity and activity of the carriers as well as intensity of the color transition. Therefore it is shown that these carriers have unquestionable advantages over common carriers of their kind. Drying temperatures have been shown to have no effect on properties of pellets except for a change in their size. Results were confirmed by statistical evaluation using ANOVA and PCA.

• Klíčová slova
• Detection, Immobilization, Neusilin, Pellets, Physostigmine, Sarin,
• MeSH
• butyrylcholinesterasa chemie   MeSH
• celulosa chemie   MeSH
• cholinesterasové inhibitory chemie   MeSH
• enzymy imobilizované chemie   MeSH
• fysostigmin chemie   MeSH
• lékové formy MeSH
• nosiče léků chemie   MeSH
• pomocné látky chemie   MeSH
• poréznost MeSH
• povidon chemie   MeSH
• sarin MeSH
• silikáty chemie   MeSH
• sloučeniny hliníku chemie   MeSH
• sloučeniny hořčíku chemie   MeSH
• tvrdost MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• aluminum magnesium silicate MeSH Prohlížeč
• butyrylcholinesterasa MeSH
• celulosa MeSH
• cholinesterasové inhibitory MeSH
• enzymy imobilizované MeSH
• fysostigmin MeSH
• lékové formy MeSH
• microcrystalline cellulose MeSH Prohlížeč
• nosiče léků MeSH
• pomocné látky MeSH
• povidon MeSH
• sarin MeSH
• silikáty MeSH
• sloučeniny hliníku MeSH
• sloučeniny hořčíku MeSH

Liquisolid systems are an innovative dosage form used for enhancing dissolution rate and improving in vivo bioavailability of poorly soluble drugs. These formulations require specific evaluation methods for their quality assurance (e.g., evaluation of angle of slide, contact angle, or water absorption ratio). The presented study is focused on the preparation, modern in vitro testing, and evaluation of differences of liquisolid systems containing varying amounts of a drug in liquid state (polyethylene glycol 400 solution of rosuvastatin) in relation to an aluminometasilicate carrier (Neusilin US2). Liquisolid powders used for the formulation of final tablets were prepared using two different methods: simple blending and spraying of drug solution onto a carrier in fluid bed equipment. The obtained results imply that the amount of liquid phase in relation to carrier material had an effect on the hardness, friability, and disintegration of tablets, as well as their height. The use of spraying technique enhanced flow properties of the prepared mixtures, increased hardness values, decreased friability, and improved homogeneity of the final dosage form.

• MeSH
• kyseliny stearové chemie   MeSH
• laktosa chemie   MeSH
• lidé MeSH
• polyethylenglykoly chemie   MeSH
• rosuvastatin kalcium chemie   MeSH
• silikáty chemie   MeSH
• sloučeniny hliníku chemie   MeSH
• sloučeniny hořčíku chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• aluminum magnesium silicate MeSH Prohlížeč
• kyseliny stearové MeSH
• laktosa MeSH
• polyethylene glycol 400 MeSH Prohlížeč
• polyethylenglykoly MeSH
• rosuvastatin kalcium MeSH
• silikáty MeSH
• sloučeniny hliníku MeSH
• sloučeniny hořčíku MeSH
• stearic acid MeSH Prohlížeč

Pharmaceutical technology offers various dosage forms that can be applied interdisciplinary. One of them are spherical pellets which could be utilized as a carrier in emerging second-generation detection tubes. This detection system requires carriers with high specific surface area (SSA), which should allow better adsorption of toxic substances and detection reagents. In this study, a magnesium aluminometasilicate with high SSA was utilized along with various concentrations of volatile substances (menthol, camphor and ammonium bicarbonate) to increase further the carrier SSA after their sublimation. The samples were evaluated in terms of physicochemical parameters, their morphology was assessed by scanning electron microscopy, and the Brunauer-Emmett-Teller (BET) method was utilized to measure SSA. The samples were then impregnated with a detection reagent o-phenylenediamine-pyronine and tested with diphosgene. Only samples prepared using menthol or camphor were found to show red fluorescence under the UV light in addition to the eye-visible red-violet color. This allowed the detection of diphosgene/phosgene at a concentration of only 0.1 mg/m3 in the air for samples M20.0 and C20.0 with their SSA higher than 115 m2/g, thus exceeding the sensitivity of the first-generation DT-12 detection tube.

• Klíčová slova
• BET method, chemical warfare agent, detection tube, extrusion, metasilicate, phosgene, porous pellets, spheronization, volatile substance,
• Publikační typ
• časopisecké články MeSH

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.

• Klíčová slova
• Co-milling, Cyclosporine A, Drug loading, Liquisolid systems, Mesoporous carrier,
• MeSH
• difrakce rentgenového záření MeSH
• pomocné látky * MeSH
• poréznost MeSH
• rozpustnost MeSH
• voda * MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• pomocné látky * MeSH
• voda * MeSH