Modulating drug release with cyclodextrins in hydroxypropyl methylcellulose gels and tablets

Area of Science:

• Pharmaceutical Sciences
• Materials Science

Background:

• Hydrophilic polymers like HPMC K4M are widely used in drug delivery.
• Cyclodextrins (CDs) are known to modify drug solubility and release profiles.

Purpose of the Study:

• To investigate the impact of beta-cyclodextrin (beta-CD) and hydroxypropyl-beta-cyclodextrin (HP-beta-CD) on drug diffusion and release from HPMC K4M gels and matrix tablets.
• To elucidate the role of drug-to-CD ratios and polymer concentration on drug release kinetics.

Main Methods:

• Preparation of HPMC K4M gels and matrix tablets with varying drug/CD ratios.
• Measurement of gel viscosity, cloud point, and drug diffusion coefficients.
• Analysis of drug release from matrix tablets using a simplex centroid design.

Main Results:

• Gel viscosity was primarily influenced by HPMC K4M concentration, affecting drug diffusion.
• In concentrated gels (2.0% HPMC K4M), high drug/CD ratios enhanced diffusion, while low ratios and excess HP-beta-CD hindered it.
• CDs promoted dissolution of hydrophobic drugs but decreased release of hydrophilic drugs from matrix tablets.

Conclusions:

• CDs can modulate drug release from HPMC K4M systems, with effects dependent on drug hydrophilicity and CD properties.
• The balance between dissolution enhancement and diffusion modification by CDs is crucial for controlling drug release.
• HP-beta-CD and beta-CD offer tunable strategies for optimizing drug delivery from polymeric matrices.