Enhanced solubility of Albendazole in Cyclodextrin Inclusion Complex: A Molecular Modeling Approach and Physicochemical Evaluation

Background Albendazole (ABZ) is the drug of choice for the treatment of a variety of human and veterinary parasites. However, it has low aqueous solubility and low bioavailability. Cyclodextrins (CD) are pharmaceutical excipients with the ability to modulate the solubilization property of hydrophobic molecules. Objective To analyze (Autodock Vina software and CycloMolder platform) the formation of inclusion complexes between ABZ, β-cyclodextrin (β-CD) and its derivatives, Methyl-β-cyclodextrin (M-β-CD) and Hydroxypropyl-β-cyclodextrin (HP-β-CD), through in vitro and in silico studies. Methods The most stable inclusion complexes were produced by the kneading method and characterized by Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), X-Ray Diffraction (XRD), determination of the ABZ content, and in vitro dissolution profile. Results Molecular modeling revealed that inclusion complexes between HP-β-CD:ABZ (in the proportion 1:1 and 2:1) presented the lowest formation energy and the highest number of intermolecular interactions, showing that the use of more cyclodextrins does not provide any gain in the stability of the complex. Through the characterization tests, the complexes experimentally obtained by kneading method demonstrated a highly suggestive method, including ABZ in HP-β-CD in both molar proportions; The results of this study showed suppression of bands in the infrared spectrum, displacement of the drug's melting temperature in DSC, crystallinity halos instead of the characteristic peaks of ABZ crystals in the XRD and a release of more than 80% of ABZ in less than 5 minutes, beyond dissolution efficiency of up to 92%. Conclusion In silico studies provided a rational selection of the appropriate cyclodextrin, enabling the elaboration of more targeted complexes, decreasing time and costs to elaborate on new formulations that increase the oral biodisponibility of ABZ.