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2000
Volume 32, Issue 14
  • ISSN: 1381-6128
  • E-ISSN: 1873-4286

Abstract

Introduction

Canagliflozin hemihydrate (CANA), an antidiabetic drug that functions as a sodium-glucose co-transporter 2 (SGLT2) inhibitor, is classified under the Biopharmaceutical Classification System (BCS) as a Class IV drug, characterized by low solubility and low permeability. This study aimed to enhance the solubility, dissolution, and permeability of CANA by preparing its inclusion complexes with α-cyclodextrin (α-CD) and β-cyclodextrin (β-CD), followed by characterization of their crystalline and biopharmaceutical properties.

Methods

The solubility of CANA in aqueous medium and phase solubility with α and β-cyclodextrin were conducted. The inclusion complexes in different CANA: α-CD ratios (1:0.25 to 1:6 mM) and CANA: β-CD ratios (1:0.50 to 1:8 mM) were prepared using the freeze-drying method. The complexes were subjected to drug content analysis, Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRPD), angle-dispersive X-ray diffraction (ADXRD), dissolution, and permeation studies.

Results

Phase solubility study indicated significant improvements in aqueous solubility of CANA with α-CD and β-CD. The solubility of CANA increased significantly (more than 100-fold in BCD8 with 0.577 mg/mL) upon complexation. BCD8 (1:7) with 97.366% and ACD6 (1:4) with 94.6% showed the highest % drug content. FTIR confirmed interactions between CANA and CDs due to the disappearance or shifting of some characteristic peaks (., 3390.68 to 3268.91 cm-1 and 1078.07 to 1024.06 cm-1 in ACD6, while 3265.05 to 3268.91 cm−1 and 1025.99 to 1024.06 cm−1 in ACD7).

Discussion

XRPD and ADXRD showed the crystalline nature of CANA and CDs, while the complexes exhibited amorphization with diffused peaks. The lowest crystallite size was observed in ACD6 (449.688) and the highest in ACD3 (966.936 Å). D-spacing was found to be smallest in ACD8 (0.722 Å) and BCD6 (4.080 Å), and the highest in ACD1 (7.276 Å), BCD7, and BCD8 (7.063 Å). The drug release ranged from 64.265% (ACD3) to 94.306% (BCD7) and increased with lower crystallinity. ACD8 (87.33%) and BCD7 (93.41%) exhibited the highest % of drug permeability.

Conclusion

Inclusion complexation with α-CD and β-CD significantly improved the solubility and dissolution of CANA in aqueous medium. These findings suggest that cyclodextrin-based inclusion complexes offer a promising approach to enhancing the biopharmaceutical performance of poorly soluble drugs, such as CANA.

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2025-08-15
2026-03-05

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Inclusion Complexes of α and β-cyclodextrin with Canagliflozin Hemihydrate: Design and Characterization
Curr. Pharm. Des. 32, 1107 (2026); https://doi.org/10.2174/0113816128384484250729091344
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  • Article Type:     Research Article
Keyword(s): ADXRD; Canagliflozin hemihydrate; crystallinity; cyclodextrin; FTIR; permeability; solubility; XRPD

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