Myricetin Amorphous Solid Dispersions-Antineurodegenerative Potential.

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Neuroscience

Background:

• Myricetin (MYR) exhibits promising antioxidant and neuroprotective properties but suffers from poor solubility and dissolution rate.
• Amorphous solid dispersions (ASDs) are a strategy to enhance the bioavailability of poorly soluble drugs.

Purpose of the Study:

• To develop an amorphous solid dispersion (ASD) of myricetin (MYR) with Polyvinylpyrrolidone K30 (PVP30).
• To enhance the solubility, dissolution rate, antioxidant, and neuroprotective properties of myricetin.
• To evaluate the stability and potential of MYR-PVP ASDs for treating neurodegenerative diseases.

Main Methods:

• Amorphous solid dispersions (ASDs) were prepared using solvent evaporation and freeze-drying techniques.
• Characterization involved X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FT-IR), and high-performance liquid chromatography (HPLC).
• Solubility, dissolution, antioxidant (ABTS, DPPH, CUPRAC, FRAP), and neuroprotective (AChE, BChE inhibition) activities were assessed. Molecular docking was employed to understand interactions.

Main Results:

• Complete amorphization of myricetin was achieved in MYR-PVP ASDs at weight ratios of 1:8 and 1:9, confirmed by XRPD and DSC.
• FT-IR and molecular modeling indicated hydrogen bonds stabilized the amorphous state, with HPLC confirming no degradation products.
• The MYR-PVP 1:9 ASD exhibited significantly improved solubility, dissolution rate, antioxidant capacity, and in vitro neuroprotective activity compared to pure myricetin.
• Molecular docking studies elucidated the interactions responsible for the inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE).
• The MYR-PVP 1:9 ASD demonstrated good physical stability under ambient conditions for two months.

Conclusions:

• Amorphous solid dispersions of myricetin with PVP K30 effectively enhance its solubility, antioxidant, and neuroprotective properties.
• The MYR-PVP 1:9 ASD is a promising system for myricetin delivery, potentially useful in managing neurodegenerative diseases.
• The developed ASDs offer a viable strategy for improving the therapeutic efficacy of myricetin.