Informace o publikaci

Investigation of Dissolution Behavior HPMC/Eudragit®/Magnesium Aluminometasilicate Oral Matrices Based on NMR Solid-State Spectroscopy and Dynamic Characteristics of Gel Layer

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NAISEROVÁ M. KUBOVÁ K. VYSLOUŽIL Jakub PAVLOKOVÁ S. VETCHÝ D. URBANOVÁ M. BRUS J. VYSLOUŽIL Jan KULICH P.

Rok publikování 2018
Druh Článek v odborném periodiku
Časopis / Zdroj AAPS PHARMSCITECH
Fakulta / Pracoviště MU

Přírodovědecká fakulta

Citace
Doi http://dx.doi.org/10.1208/s12249-017-0870-6
Obor Biochemie
Klíčová slova matrix tablets HPMC Eudragit® NE30D Neusilin® US2 gel layer Levetiracetam Burst effect thermal treatment multivariate data analysis
Popis 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.

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