Controlling the Solubility, Release Rate and Permeation of Riluzole with Cyclodextrins

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Physical Chemistry

Background:

• Riluzole (RLZ), a BCS class II drug, exhibits poor aqueous solubility, limiting its therapeutic efficacy.
• Improving solubility and modulating permeability are crucial for enhancing drug absorption and bioavailability.
• Cyclodextrins (CDs) are widely used excipients for complexation to improve drug properties.

Purpose of the Study:

• To investigate the complexation of Riluzole (RLZ) with alpha-cyclodextrin (α-CD) and sulfobutylether-β-cyclodextrin (SBE-β-CD).
• To evaluate the impact of cyclodextrin complexation on RLZ solubility, dissolution rate, and membrane permeability.
• To explore synergistic effects of CDs and polymers on RLZ delivery.

Main Methods:

• Complexation studies of RLZ with α-CD and SBE-β-CD.
• Solubility and stability constant determination.
• In vitro membrane permeability studies using artificial membranes (cellulose, PermeaPad, polydimethylsiloxane-polycarbonate).
• Preparation and characterization of solid RLZ/CD complexes.

Main Results:

• SBE-β-CD demonstrated a higher affinity for RLZ than α-CD, with stability constants indicating stronger complex formation.
• RLZ solubility increased 1.7-fold with α-CD and 3.7-fold with SBE-β-CD at 1% CD concentration.
• Co-formulation with certain polymers (PG, PEG400, PEG1000) enhanced solubility with α-CD while maintaining permeability.
• Permeation rates varied significantly across different artificial membranes, with maximal rates observed across hydrophilic cellulose membranes.

Conclusions:

• Cyclodextrin complexation, particularly with SBE-β-CD, effectively enhances Riluzole solubility.
• The choice of cyclodextrin and co-excipients influences drug solubility and permeability profiles.
• Understanding permeation characteristics across different membranes is vital for predicting in vivo drug absorption and optimizing delivery strategies.