scholarly journals Sustained-Release Solid Dispersion of High-Melting-Point and Insoluble Resveratrol Prepared through Hot Melt Extrusion to Improve Its Solubility and Bioavailability

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 4982
Author(s):  
Wenjing Zhu ◽  
Wenling Fan ◽  
Xiaotong Zhang ◽  
Meiqi Gao
Keyword(s):  
Melting Point ◽  
Sustained Release ◽  
Solid Dispersion ◽  
Hot Melt Extrusion ◽  
High Melting ◽  
Melt Extrusion ◽  
High Melting Point ◽  
Hot Melt ◽  
Polymeric Blend

This study aimed to prepare a sustained-release solid dispersion of poorly water-soluble resveratrol (RES) with high melting point in a single hot melt extrusion step. A hydrophobic–hydrophilic polymeric blend (Eudragit RS and PEG6000) was used to control the release of RES. With the dispersive mixing and high shear forces of hot melt extrusion, the thermodynamic properties and dispersion of RES were changed to improve its solubility. The effects of the formulation were investigated through univariate analysis to optimize the preparation of the sustained-release solid dispersion. In vitro and in vivo studies were performed to evaluate the prepared RES/RS/PEG6000 sustained-release solid dispersion. The physical state of the solid dispersion was characterized using differential scanning calorimetry and X-ray diffraction. Surface properties of the dispersion were visualized using scanning electron microscopy, and the chemical interaction between RES and excipients was detected through Fourier-transform infrared spectroscopy. Results suggested that the optimized sustained-release solid dispersion was obtained when the mass ratio of RES-polymeric blend was 1:5, the ratio of PEG6000 was 35%, the barrel temperature was 170 °C, and the screw speed was 80 rpm. In vitro studies demonstrated that the solid dispersion showed a good sustained release effect. The cumulative release of RES reached 82.42% until 12 h and was fit by the Weibull model. In addition, the saturated solubility was 2.28 times higher than that of the bulk RES. In vitro studies demonstrated that the half-life increased from 3.78 to 7.09 h, and the bioavailability improved to 140.38%. The crystalline RES was transformed into the amorphous one, and RES was highly dispersed in the polymeric blend matrix.

Solvent-Assisted Hot Melt Extrusion of a Thermally Labile, High Melting Point Compound

2021 ◽  
Vol 22 (7) ◽  
Author(s):  
C. Lagan ◽  
J. E. Huckle ◽  
J. M. Katz ◽  
B. Khorsand ◽  
D. Daurio ◽  
...  
Keyword(s):  
Melting Point ◽  
Hot Melt Extrusion ◽  
High Melting ◽  
Melt Extrusion ◽  
High Melting Point ◽  
Hot Melt

Fenofibrate Solid Dispersion Processed by Hot-Melt Extrusion: Elevated Bioavailability and Its Cell Transport Mechanism

2019 ◽  
Vol 16 (6) ◽  
pp. 538-547 ◽  
Author(s):  
Ting Wen ◽  
Boyi Niu ◽  
Qiaoli Wu ◽  
Yixian Zhou ◽  
Xin Pan ◽  
...  
Keyword(s):  
Solid Dispersion ◽  
Amorphous Solid ◽  
Hot Melt Extrusion ◽  
In Vitro Dissolution ◽  
Amorphous Solid Dispersion ◽  
Dissolution Test ◽  
Melt Extrusion ◽  
Cell Transport ◽  
Hot Melt

Background: Fenofibrate (FNB) is an effective drug for the treatment of hypertriglyceridemia, hypercholesterolemia as well as mixed hyperlipidemia. However, due to its poor aqueous solubility, FNB has the problem of poor oral absorption followed by low bioavailability. Objective: The aim of this research was to construct FNB amorphous solid dispersion employing PVP VA64 as the carrier by hot-melt extrusion method, in order to improve the oral bioavailability. Additionally, the cell transport experiment was conducted to further investigate the mechanism of promoted osmotic absorption. Methods: The physical state of the obtained solid dispersion was characterized using SEM, DSC and XRD. Besides, in vitro Caco-2 cells were used to evaluate the cytotoxicity of the carrier and mimic gastrointestinal drug permeation. At last, in vitro dissolution test and in vivo bioavailability study were also carried out. Results: The prepared FNB solid dispersion was found to be an amorphous state after hot-melt extrusion process. In vitro cytotoxicity test on Caco-2 cells confirmed the excellent biocompatibility of the carrier PVP VA64. Besides, transwell cell transport assay and in vitro dissolution test revealed that FNB released from amorphous solid dispersion was equipped with an improved transmembrane transport and dissolution rate. Moreover, pharmacokinetic study in beagle dogs showed that comparing with commercial micronized product Lipanthyl®, the oral bioavailability of FNB solid dispersion was significantly enhanced (2.45 fold). Conclusion: In conclusion, PVP VA64 can be regarded as a promising polymer to enhance the bioavailability of poorly water-soluble drugs such as FNB processed by hot-melt extrusion. Besides, investigations on the mechanism of the enhanced penetration are expected to lay a foundation on the subsequent development of effective and practical solid dispersion.

Melt Extrusion for a High Melting Point Compound with Improved Solubility and Sustained Release

2017 ◽  
Vol 19 (1) ◽  
pp. 358-370 ◽  
Author(s):  
Jiannan Lu ◽  
Sakae Obara ◽  
Fei Liu ◽  
Wanyi Fu ◽  
Wen Zhang ◽  
...  
Keyword(s):  
Melting Point ◽  
Sustained Release ◽  
High Melting ◽  
Melt Extrusion ◽  
High Melting Point

scholarly journals Development and Characterization of Sustained-Released Donepezil Hydrochloride Solid Dispersions Using Hot Melt Extrusion Technology

Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 213
Author(s):  
Abdullah Alshetaili ◽  
Bjad K. Almutairy ◽  
Sultan M. Alshehri ◽  
Michael A. Repka
Keyword(s):  
Drug Release ◽  
Sustained Release ◽  
Solid Dispersion ◽  
Hot Melt Extrusion ◽  
Release Profile ◽  
Release Behavior ◽  
Melt Extrusion ◽  
Sustained Release Formulation ◽  
Donepezil Hydrochloride ◽  
Hot Melt

The aim of this work was to develop the sustained release formulation of donepezil hydrochloride (DH) using the hot-melt extruded solid dispersion technique via the rational screening of hydrophobic carriers. Hydrophobic carriers with different physicochemical properties such as pH-independent swellability, low-permeability (Eudragit® RS PO (E-RS)), pH-independent non-swellability (ethyl cellulose N7 (EC-N7)), and the presence of lipids (Compritol® 888 ATO (C-888)) with or without pore-forming agents were used to achieve the sustained release profile of DH. Mannitol (MNT) was chosen as the temporary pore-forming agent. The thermal analysis showed that both the drug and C-888 preserved their crystallinity within a solid dispersion. During a dissolution test, MNT could generate pores, and the drug release rate was proportionally correlated to the MNT content. Tailoring of the ratio of C-888 and MNT in the formulations along with an appropriate extrusion temperature profile resulted in the modified release of DH, and a preferable release pattern was obtained under these conditions. C-888 was chosen for the further investigations to obtain tablets with a high integrity. The optimized tablets were compared to the marketed formulation of Aricept® in terms of drug release profiles. The optimized formulation showed the stable and sustained release behavior of extended release profile, which was close to the release behavior of Aricept® with good tablet characteristics. It was concluded that the hot-melt extrusion technique can be utilized for the manufacturing of DH sustained release tablets with improved tablet integrity and characteristics by co-processing the tablet excipient with DH/C-888.

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