Hot-Melt Extrusion as an Effective Technique for Obtaining an Amorphous System of Curcumin and Piperine with Improved Properties Essential for Their Better Biological Activities

Abstract

Poor bioavailability hampers the use of curcumin and piperine as biologically active agents. It can be improved by enhancing the solubility as well as by using bioenhancers to inhibit metabolic transformation processes. Obtaining an amorphous system of curcumin and piperine can lead to the overcoming of these limitations. Hot-melt extrusion successfully produced their amorphous systems, as shown by XRPD and DSC analyses. Additionally, the presence of intermolecular interactions between the components of the systems was investigated using the FT-IR/ATR technique. The systems were able to produce a supersaturation state as well as improve the apparent solubilities of curcumin and piperine by 9496- and 161-fold, respectively. The permeabilities of curcumin in the GIT and BBB PAMPA models increased by 12578- and 3069-fold, respectively, whereas piperine’s were raised by 343- and 164-fold, respectively. Improved solubility had a positive effect on both antioxidant and anti-butyrylcholinesterase activities. The best system suppressed 96.97 ± 1.32% of DPPH radicals, and butyrylcholinesterase activity was inhibited by 98.52 ± 0.87%. In conclusion, amorphization remarkably increased the dissolution rate, apparent solubility, permeability, and biological activities of curcumin and piperine.

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

“…In addition, the carbonyl peak of PVP K30 shifted from FT-IR spectra of the various systems investigated are presented in Figure 7. The differences between the crystalline and amorphous spectra of curcumin and hesperetin have already been described [42,43].…”

Myricetin Amorphous Solid Dispersions—Antineurodegenerative Potential

“…PVP acts as a hydrophilic polymer that can form a stable molecular dispersion with polyphenols, thereby preventing their crystallization and maintaining them in an amorphous state. It was confirmed that the amorphous form of the polyphenols has a significantly higher solubility compared to its crystalline counterpart [ 45 , 46 , 48 , 55 , 56 , 57 , 58 ]. Therefore, this study attempts to obtain an amorphous solid dispersion (ASD) of myricetin (MYR, Figure 1 b) with PVP K30 (PVP30).…”

“…Amorphous materials lack long-range order in their atomic arrangement, while crystalline materials exhibit a regular and repeating pattern. Confirming the amorphous/crystalline nature of a substance is crucial as it affects its physical and chemical properties, including solubility, stability, and bioavailability [ 46 , 47 , 48 , 50 , 55 , 56 , 59 ].…”

“…Additionally, researchers show that a single glass transition seen in an amorphous dispersion’s thermogram indicates complete miscibility [ 50 , 66 , 67 ]. For instance, based on thermal analysis, the full miscibility of curcumin-piperine-PVP VA64 [ 55 ], genistein-amino acids [ 68 ], hesperidin-Soluplus ® and hesperidin-HPMC [ 46 ], hesperetin-piperine-PVPVA64 [ 48 ], kaempferol-Eudragit ® [ 46 ], pterostilbene-Soluplus ® [ 50 ], and tannic acid-poly(ε-caprolactone) [ 69 ] were confirmed.…”

“…Compared to their crystalline counterparts, amorphous polyphenols frequently have better solubility and dissolution rates. Improved bioavailability and therapeutic effectiveness may result from this increased solubility [ 46 , 47 , 48 , 50 , 55 ].…”