aluminometasilicates
Dotaz
Zobrazit nápovědu
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.
- MeSH
- difrakce rentgenového záření MeSH
- pomocné látky * MeSH
- poréznost MeSH
- rozpustnost MeSH
- voda * MeSH
- Publikační typ
- časopisecké články 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.
- Publikační typ
- časopisecké články 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.
- Publikační typ
- časopisecké články MeSH
Modern pharmaceutical technology still seeks new excipients and investigates the further use in already known ones. An example is magnesium aluminometasilicate Neusilin® US2 (NEU), a commonly used inert filler with unique properties that are usable in various pharmaceutical fields of interest. We aimed to explore its application in hypromellose matrix systems (HPMC content 10-30%) compared to the traditionally used microcrystalline cellulose (MCC) PH 102. The properties of powder mixtures and directly compressed tablets containing individual fillers NEU or MCC, or their blend with ratios of 1.5:1, 1:1, and 0.5:1 were investigated. Besides the routine pharmaceutical testing, we have enriched the matrices' evaluation with a biorelevant dynamic dissolution study and advanced statistical analysis. Under the USP apparatus 2 dissolution test, NEU, individually, did not provide advantages compared to MCC. The primary limitations were the burst effect increase followed by faster drug release at the 10-20% HPMC concentrations. However, the biorelevant dynamic dissolution study did not confirm these findings and showed similarities in dissolution profiles. It indicates the limitations of pharmacopoeial methods in matrix tablet development. Surprisingly, the NEU/MCC blend matrices at the same HPMC concentration showed technologically advantageous properties. Besides improved flowability, tablet hardness, and a positive impact on the in vitro drug dissolution profile toward zero-order kinetics, the USP 2 dissolution data of the samples N75M50 and N50M50 showed a similarity to those obtained from the dynamic biorelevant apparatus with multi-compartment structure. This finding demonstrates the more predictable in vivo behaviour of the developed matrix systems in human organisms.
- Publikační typ
- časopisecké články MeSH
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.
- 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.
- MeSH
- hořčík * MeSH
- oxid křemičitý * MeSH
- prášky, zásypy, pudry MeSH
- příprava léků MeSH
- rozpustnost MeSH
- tablety MeSH
- 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.
- 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
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.
- 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
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.
- 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
Jednou z moderních technologií jak zajistit dostatečnou biologickou dostupnost léčiv s omezenou rozpustností ve vodném prostředí představuje příprava systémů kapalina v pevné fázi, neboli liquisolid systémů. Funkčním principem těchto formulací je nasorbování léčiva v kapalné formě na porézní nosič (aluminometasilikáty, mikrokrystalická celulosa atd.). Po přidání dalších pomocných látek, především obalovacího materiálu (koloidní oxid křemičitý), dochází ke vzniku prášku s vlastnostmi vhodnými pro převod na běžné jednotkové pevné lékové formy pro perorální podání (tablety, tobolky). Léčivo je v pak do organismu podáváno již v rozpuštěném stavu a navíc vysoký měrný povrch použitých excipientů a hydrofilizace jejich povrchů použitým rozpouštědlem usnadňuje jeho kontakt s a přechod do disolučního média i trávicích tekutin. Tato technologie představuje pro svou jednoduchost přípravy zajímavou alternativu k v současnosti používaným postupům. Článek navazuje popisem konkrétních aspektů ovlivňujících přípravu systémů kapalina v pevné fázi na již publikované práce o biologické dostupnosti léčiv a možnostech jejího technologického ovlivňování.
One of the modern technologies of how to ensure sufficient bioavailability of drugs with limited water solubility is represented by the preparation of liquisolid systems. The functional principle of these formulations is the sorption of a drug in a liquid phase to a porous carrier (aluminometasilicates, microcrystalline cellulose, etc.). After addition of further excipients, in particular a coating material (colloidal silica), a powder is formed with the properties suitable for conversion to conventional solid unit dosage forms for oral administration (tablets, capsules). The drug is subsequently administered to the GIT already in a dissolved state, and moreover, the high surface area of the excipients and their surface hydrophilization by the solvent used, facilitates its contact with and release to the dissolution medium and GI fluids. This technology, due to its ease of preparation, represents an interesting alternative to the currently used methods of bioavailability improvement. The article follows up, by describing the specific aspects influencing the preparation of liquid systems, on the already published papers about the bioavailability of drugs and the possibilities of its technological improvement.
- Klíčová slova
- liquisolid systémy, preformulační studie, porézní nosič, systémy kapalina v pevné fázi,
- MeSH
- biologická dostupnost MeSH
- farmaceutická chemie * MeSH
- léky s prodlouženým účinkem MeSH
- nosiče léků MeSH
- poréznost MeSH
- prášky, zásypy, pudry * MeSH
- příprava léků MeSH
- rozpouštědla MeSH
- rozpustnost MeSH
- stabilita léku MeSH
- tablety * MeSH
- tobolky MeSH
- uvolňování léčiv MeSH
- Publikační typ
- přehledy MeSH
