PVP VA64 as a novel release-modifier for sustained-release mini-matrices prepared via hot melt extrusion

The purpose of this study was to explore poly(vinylpyrrolidone-co-vinyl acetate) (PVP VA64) as a novel release-modifier to tailor the drug release from ethylcellulose (EC)-based mini-matrices prepared via hot melt extrusion (HME). Quetiapine fumarate (QF) was selected as model drug. QF/EC/PVP VA64 mini-matrices were extruded with 30% drug loading. The physical state of QF in extruded mini-matrices was characterized using differential scanning calorimetry, X-ray powder diffraction, and confocal Raman microscopy. The release-controlled ability of PVP VA64 was investigated and compared with that of xanthan gum, crospovidone, and low-substituted hydroxypropylcellulose. The influences of PVP VA64 content and processing temperature on QF release behavior and mechanism were also studied. The results indicated QF dispersed as the crystalline state in all mini-matrices. The release of QF from EC was very slow as only 4% QF was released in 24 h. PVP VA64 exhibited the best ability to enhance the drug release as compared with other three release-modifiers. The drug release increased to 50–100% in 24 h with the addition of 20–40% PVP VA64. Increasing processing temperature slightly slowed down the drug release by decreasing free volume and pore size. The release kinetics showed good fit with the Ritger-Peppas model. The values of release exponent (n) increased as PVP VA64 is added (0.14 for pure EC, 0.41 for 20% PVP VA64, and 0.61 for 40% PVP VA64), revealing that the addition of PVP VA64 enhanced the erosion mechanism. This work presented a new polymer blend system of EC with PVP VA64 for sustained-release prepared via HME.



PVP VA64 was approved to be a novel drug release- modifier for EC-based mini-matrices prepared via hot melt extrusion. QF was selected as the model drug. PVP VA64 has the highest ability to accelerate QF release from EC in comparison with xanthan gum, CPVP, and L-HPC (three extensively used release-modifier). The addition of 40% PVP VA64 dramatically enhanced QF release from 4 to 100% in 24 h. Increasing processing temperature slightly slowed down the QF release due to the improved mixing and the decreased pore size. The release kinetics of QF/EC/ PVP VA64 mini-matrices showed good fit with the Ritger- Peppas model. The increase of PVP VA64 in the formula- tion enhanced the erosion mechanism. EC/PVP VA64 was a novel polymer blend system for sustained release prepared via HME.


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