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

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62157124%3A16370%2F18%3A43876650" target="_blank" >RIV/62157124:16370/18:43876650 - isvavai.cz</a>

Result on the web

<a href="http://dx.doi.org/10.1208/s12249-017-0870-6" target="_blank" >http://dx.doi.org/10.1208/s12249-017-0870-6</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1208/s12249-017-0870-6" target="_blank" >10.1208/s12249-017-0870-6</a>

Result language

angličtina

Original language name

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

Original language description

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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30104 - Pharmacology and pharmacy

Project

—

Continuities

S - Specificky vyzkum na vysokych skolach

Publication year

2018

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

AAPS PharmSciTech

ISSN

1530-9932

e-ISSN

—

Volume of the periodical

19

Issue of the periodical within the volume

2

Country of publishing house

US - UNITED STATES

Number of pages

12

Pages from-to

681-692

UT code for WoS article

000423720400017

EID of the result in the Scopus database

2-s2.0-85032201452