Detection tubes are small devices for the colorimetric enzymatic detection of cholinesterase inhibitors such as sarin, soman, VX nerve agents and substances denoted as Novichok. These detectors contain carriers in the form of pellets with immobilized cholinesterase, substrate and detection reagent. Their advantages are portability, sensitivity and simplicity, enabling fast detection of such compounds from air and water in case of a terrorist attack or war. In general, maintaining the stability of an enzyme for a longer time is very problematic; therefore, its further enhancement is required for safety and financial reasons. In this study, the stability of our patented carriers in the form of pellets with immobilized butyrylcholinesterase containing an increasing amount of the unique sorbent Neusilin® US2 was evaluated. The samples containing Neusilin maintained the stability of the immobilized enzyme for a longer time even at higher temperature and humidity than the currently commercially used carrier without Neusilin, allowing improved detection of nerve agents.

• Klíčová slova
• Cholinesterase, Detection, Enzyme, Nerve agent, Neusilin, Stability,
• MeSH
• biosenzitivní techniky metody   MeSH
• butyrylcholinesterasa chemie   metabolismus   MeSH
• cholinesterasové inhibitory analýza   MeSH
• enzymy imobilizované chemie   metabolismus   MeSH
• kolorimetrie metody   MeSH
• nosiče léků chemie   MeSH
• silikáty metabolismus   MeSH
• sloučeniny hliníku metabolismus   MeSH
• sloučeniny hořčíku metabolismus   MeSH
• stabilita enzymů účinky léků   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• aluminum magnesium silicate MeSH Prohlížeč
• butyrylcholinesterasa MeSH
• cholinesterasové inhibitory MeSH
• enzymy imobilizované MeSH
• nosiče léků MeSH
• silikáty MeSH
• sloučeniny hliníku MeSH
• sloučeniny hořčíku 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