Cyclodextrin Complexation Using Sbe-Β-Cd Induces the Solubility and Bioavailability of Diclofenac Sodium for Drug Delivery
Ikram Ullah Khan 1*
Biosensors and Nanotheranostics 3(1) 1-7 https://doi.org/10.25163/biosensors.317340
Submitted: 11 February 2024 Revised: 13 April 2024 Published: 15 April 2024
Abstract
Background: Diclofenac sodium (DS) is a poorly water-soluble drug, especially in gastric juice (15 µg/ml), which can lead to harmful effects on the gastric mucosa, including gastrointestinal bleeding after oral administration. The aim of this study was to evaluate the impact of natural and modified cyclodextrins on improving the solubility of diclofenac sodium in acidified aqueous solutions, and to confirm the formation of solid inclusion complexes between diclofenac sodium and cyclodextrins using different preparation techniques. Methods: Inclusion complexes were prepared in both solution and solid states using β-CD, HP-β-CD, Me-β-CD, HP-γ-CD, and SBE-β-CD. The solid-inclusion mixtures were obtained through dry grinding (physical mixtures), kneading, co-precipitation, and freeze-drying in a 1:1 molar ratio, and were characterized by PXRD and ATR-FTIR analyses. Results: The phase solubility isotherms revealed that the solubility of diclofenac sodium increased with higher concentrations of cyclodextrins, with the isotherms classified as AL type, indicating a 1:1 stoichiometric complexation. The stability constants (KS) ranged from 1088.8 ± 8.33 M?¹ to 5009.57 ± 54.42 M?¹ for all tested cyclodextrins, with SBE-β-CD showing the most significant solubility enhancement. Characterization of the binary systems by XRD and FTIR confirmed the formation of inclusion complexes, particularly in mixtures prepared by kneading, freeze-drying, and co-precipitation, as evidenced by the disappearance of drug crystallinity peaks (indicating amorphization) and alterations in the characteristic bands of the guest molecule. Conclusion: This study demonstrates that complexation with cyclodextrins is an effective strategy for enhancing the solubility of diclofenac sodium, with freeze-drying identified as the most promising method for forming stable inclusion compounds. Moreover, these strategies can be optimized for potential nanoparticale based drug delivery systems applications.
Keywords: Diclofenac sodium, Cyclodextrin complexation, Solubility enhancement, Inclusion complexes, Freeze-drying method
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