Highly Soluble Drugs Directly Granulated by Water Dispersions of Insoluble Eudragit® Polymers as a Part of Hypromellose K100M Matrix Systems

Abstract

The aim of the present study was to investigate the suitability of insoluble Eudragit® water dispersions (NE, NM, RL, and RS) for direct high-shear granulation of very soluble levetiracetam in order to decrease its burst effect from HPMC K100M matrices. The process characteristics, ss-NMR analysis, in vitro dissolution behavior, drug release mechanism and kinetics, texture profile analysis of the gel layer, and PCA analysis were explored. An application of water dispersions directly on levetiracetam was feasible only in a multistep process. All prepared formulations exhibited a 12-hour sustained release profile characterized by a reduced burst effect in a concentration-dependent manner. No effect on swelling extent of HPMC K100M was observed in the presence of Eudragit®. Contrary, higher rigidity of formed gel layer was observed using combination of HPMC and Eudragit®. Not only the type and concentration of Eudragit®, but also the presence of the surfactant in water dispersions played a key role in the dissolution characteristics. The dissolution profile close to zero-order kinetic was achieved from the sample containing levetiracetam directly granulated by the water dispersion of Eudragit® NE (5% of solid polymer per tablet) with a relatively high amount of surfactant nonoxynol 100 (1.5%). The initial burst release of drug was reduced to 8.04% in 30 min (a 64.2% decrease) while the total amount of the released drug was retained (97.02%).

Porous Plastic Matrix Tablets of Levetiracetam for Zero-Order Controlled Release: Development and Formulation Optimization

“…It was evident from the formulations F1 and F4 that with the increase in the concentration of the plastic polymer, the drug release rate was found to be significantly decreased (p<0.05, one-way ANOVA) due to the increase in the density of the plastic polymer as well as owing to the difficulty in permeation of water into the plastic matrix at high amounts of the matrix polymers. The obtained results were correlated with those reported by Maskova E et al [23].…”

“…The rate constant values were showed in the table 3. This could be attributed to the degree of permeability of water by the polymer into the plastic polymer matrix [21][22][23]. With the increase in the permeability of water into the plastic matrix, the diffusion of the drug from the plastic matrix increases and vice versa.…”

Development of raft-forming liquid and chewable tablet formulations incorporating quercetin solid dispersions for treatment of gastric ulcers

“…The crosslinked alginate gel matrix was incapable of delaying diffusion of quercetin, following rapid dissolution from the quercetin/PVPK30 solid dispersion. Several studies have reported that the burst release effect may be reduced by increasing the concentration of polymer in the delivery system ( Chakraborty et al, 2009 , Mašková et al, 2019 ). However, the alginate solution concentration was limited to 2% w/v in the present study due to the resulting high viscosity.…”

Development of Eudragit® Nanoparticles for Intranasal Drug Delivery: Preliminary Technological and Toxicological Evaluation

“…Eudragit ® RS100 (RS) and RL100 (RL) are copolymers of poly(ethylacrylate, methylmethacrylate and chlorotrimethyl-ammonioethyl methacrylate), containing an amount of quaternary ammonium groups between 4.5 and 6.8% and 8.8 and 12% for RS and RL, respectively. Both are insoluble at physiological pH values and capable of swelling [22], thus representing good materials for the dispersions of drugs [23,24].…”