Curcumin amorphous solid dispersions benefit from hydroxypropyl methylcellulose E50 to perform enhanced...

Area of Science:

• Pharmaceutical Science
• Materials Science

Background:

• Curcumin (Cur) exhibits poor solubility and permeability, limiting its therapeutic applications.
• Amorphous solid dispersions (ASDs) are a promising strategy to enhance drug delivery.
• Eudragit EPO (EuD) and hydroxypropyl methylcellulose E50 (HPMC) are polymers investigated for ASD formulation.

Purpose of the Study:

• To investigate the role of HPMC in enhancing the solubility and permeability of curcumin amorphous solid dispersions (ASDs).
• To elucidate the mechanisms by which HPMC influences curcumin crystallization and transmembrane transport.
• To evaluate the impact of HPMC-containing ASDs on oral bioavailability and anti-inflammatory effects.

Main Methods:

• Formulation of curcumin ASDs using Eudragit EPO (EuD) and varying ratios of HPMC.
• Dynamic light scattering (DLS) to determine particle size and assess crystallization inhibition.
• Molecular dynamic (MD) modeling to study molecular interactions and aggregation behavior.
• Assessment of transmembrane permeability using phospholipid bilayer models.
• Evaluation of relative oral bioavailability and anti-inflammatory efficacy in vivo.

Main Results:

• HPMC addition reduced curcumin particle size in ASDs from >300 nm to <200 nm, inhibiting crystallization.
• MD simulations showed HPMC prevented curcumin aggregation in EuD medium.
• HPMC acted as a surfactant, disordering phospholipid bilayers and enhancing curcumin transmembrane transport.
• Cur-EuD/HPMC 3:1 ASDs demonstrated significantly improved permeability, oral bioavailability, and anti-inflammatory activity.

Conclusions:

• HPMC is a critical excipient for developing effective curcumin ASDs.
• HPMC enhances curcumin solubility and permeability through particle size reduction, crystallization inhibition, and improved transmembrane transport.
• Curcumin ASDs formulated with an optimal amount of HPMC represent a viable therapeutic strategy for medical applications.