Inclusion Complexes of α and β -cyclodextrin with Canagliflozin Hemihydrate: Design and Characterization

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery
• Physical Chemistry

Background:

• Canagliflozin hemihydrate (CANA) is a BCS Class IV antidiabetic drug with low solubility and permeability.
• Enhancing CANA's solubility and permeability is crucial for improving its therapeutic efficacy.

Purpose of the Study:

• To improve the solubility, dissolution, and permeability of CANA.
• To prepare and characterize inclusion complexes of CANA with alpha-cyclodextrin (α-CD) and beta-cyclodextrin (β-CD).

Main Methods:

• Phase solubility studies were conducted to assess CANA solubility with α-CD and β-CD.
• Inclusion complexes were prepared using the freeze-drying method at various drug-to-cyclodextrin ratios.
• Characterization involved drug content analysis, FTIR, XRPD, ADXRD, in vitro dissolution, and permeation studies.

Main Results:

• Complexation with α-CD and β-CD significantly increased CANA's aqueous solubility (over 100-fold).
• FTIR confirmed drug-excipient interactions, and XRPD/ADXRD indicated amorphization of the complexes.
• Drug release and permeability were enhanced, particularly with β-cyclodextrin complexes (e.g., BCD7 and BCD8).

Conclusions:

• Cyclodextrin inclusion complexation effectively enhances the solubility and dissolution of CANA.
• These findings highlight cyclodextrin complexes as a viable strategy for improving the biopharmaceutical performance of poorly soluble drugs.