Preparation of Curcumin-Eudragit® E PO Solid Dispersions with Gradient Temperature through Hot-Melt Extrusion

Abstract

Hot-melt extrusion (HME) has great advantages for the preparation of solid dispersion (SD), for instance, it does not require any organic solvents. Nevertheless, its application to high-melting-point and thermosensitive drugs has been rarely reported. In this study, thermally unstable curcumin (Cur) was used as a drug model. The HME process was systematically studied by adjusting the gradient temperature mode and residence time, with the content, crystallinity and dissolution of Cur as the investigated factors. The effects of barrel temperature, screw speed and cooling rate on HME were also examined. Solubility parameters and the Flory–Huggins method were used to evaluate the miscibility between Cur and carriers. Differential scanning calorimetry, X-ray diffraction, Fourier transform infrared spectroscopy, equilibrium solubility and in vitro and in vivo experiments were used to characterize and evaluate the results. An amorphous Cur SD was successfully obtained, increasing the solubility and release of Cur. In the optimal process, the mass ratio of Cur to Eudragit® E PO (EPO) was 1:4 and the barrel temperature was set at a gradient heating mode (130 °C–135 °C–140 °C–145 °C–150 °C–155 °C–160 °C) at 100 rpm. Related pharmacokinetic test results also showed the improved bioavailability of the drug in rats. In a pharmacodynamic analysis of Sprague–Dawley rats, the Cmax and the bioavailability of the Cur-EPO SD were 2.6 and 1.5 times higher than those of Cur, respectively. The preparation of the amorphous SD not only provided more solubility but also improved the bioavailability of Cur, which provides an effective way to improve the bioavailability of BCS II drugs.

Sweeteners Show a Plasticizing Effect on PVP K30—A Solution for the Hot-Melt Extrusion of Fixed-Dose Amorphous Curcumin-Hesperetin Solid Dispersions

“…Fan et al indicated that curcumin extrudates obtained by the process at 160 • C showed a lower content of the active compound, which the authors attributed to partial thermal degradation under processing conditions. On the other hand, when the process was carried out at 140 • C, the presence of curcumin in partially crystalline form was found [24]. Based on the above, we determined that extrusion should be carried out at 150 • C. Bearing in mind the aforementioned findings, it is impossible to extrude curcumin using PVP K30 on its own, as the polymer shows a Tg of about 168 • C. The reason is that efficient extrusion requires that the processing temperature be at least 20 • C higher than the Tg of the extruded blend, which mainly depends on the carrier used [25][26][27].…”

Curcuma phaeocaulis Inhibits NLRP3 Inflammasome in Macrophages and Ameliorates Nanoparticle-Induced Airway Inflammation in Mice

“…This is due in part to its poor pharmacokinetic properties. However, recent advances in technology including hot-melt extrusion (HME) has significantly reduced this limitation by increasing bioavailability of curcumin [ 26 ]. In light of this fact, it would be of great significance to adopt a promising technology such as HME to enhance the solubility and bioavailability of the crude extract of C. phaeocaulis .…”

Solid Dispersion as a Potential Approach to Improve Dissolution and Bioavailability of Curcumin From Turmeric (Curcuma Longa L.)

“…In this method, exposure to the drug at high temperatures tends to be short, i.e., only for 1-2 min, so it is still possible for thermolabile materials [9]. Fan et al [40] investigated the hot melt extrusion (HME) process for the preparation of curcumin solid dispersion. The carrier used in this study is Eudragit EPO with a 20% drug load (ratio 1:4).…”

“…Critical process parameters that affect the characteristics of solid dispersion using the HME method include 1) temperature; an optimal temperature is needed to be able to change all crystalline forms to amorphous but still maintain drug stability; 2) the speed of the screw extruder, the slow speed of the screw extruder causes the drug contact time to be longer so it has the potential for degradation; 3) cooling method, amorphous solid dispersion can be produced by using the proper cooling method to avoid phase separation and drug nucleation [40,41].…”