Physicochemical characterization of multicomponent inclusion complex of efavirenz with α-cyclodextrin and meglumine

Rosario

Congreso; 7ma Reunión Internacional de Ciencias Farmacéuticas; 2023

Universidad Nacional de Rosario

Efavirenz (EFZ) is a non-nucleoside reverse transcriptase inhibitor approved for the treatment of HIV type 1 infection that exhibits low and variable oral bioavailability due to its poor aqueous solubility 1. A widely used strategy for the development of new pharmaceutical formulations with optimized physicochemical properties is the use of cyclodextrins (CDs) 2. CDs are cyclic oligosaccharides that can enhance the aqueous solubility of drugs by forming inclusion complexes.Moreover, the addition of suitable auxiliary substances can improve the solubilization capacity of CD and the complexation efficiency. In a previous work, we demonstrated that the solubility of EFZ can be improved by complexation with α-CD 3.The aim of this work was to increase the aqueous solubility of EFZ by preparing multicomponent complexes (MC) with α-CD and meglumine (MG) as a third component (EFZ:α-CD:MG) that were compared with binary complexes (EFZ:α-CD).The interactions between the components were investigated both in solution by phase-solubility analysis and in the solid state by Fourier-transform Infrared Spectroscopy (FTIR), Hot Stage Microscopy (HSM), powder X-ray diffraction (PXRD), and contact angle measurements. The binary and multicomponent complexes in solid state were prepared by the drop-assisted grinding method with a 1:1 and 1:1:1 stoichiometry ratio, respectively. In addition, the dissolution and solubility behavior of the solids were assayed.Phase solubility studies showed that EFZ solubility increased with increasing α-CD concentrations, in the presence of MG. CD and MG increased the solubility of EFZ from 17.1 μg/mL to 70 μg/Ml (efficiency of solubility, ES, 4), while the binary complex showed a ES= 2.5. FTIR and HSM studies showed differences between the MC and the pure components. PXRD patterns evidenced a decrease in the crystallinity degree of the MC. EFV, EFZ:α-CD and EFZ:α-CD:MG showed a water solubility of 2.2 ± 0.2, 30.8 ± 1.1 and 100.4 ± 6.9 μg/mL, respectively. Dissolution studies revealed that EFZ:α-CD and EFZ:α-CD:MG presented an increased extent of drug dissolved in comparison with the pure drug. The contact angles for EFZ, EFZ:α-CD and EFZ:α-CD:MG were found to be 129±3°, 101±1° and 97±1°, respectively, indicating that the presence of α-CD and MG improves the wettability of the drug. In conclusion, this study demonstrated that the formation of complexes between EFZ, α-CD and MG was a suitable strategy for enhancing the solubility and dissolution performance of the drug.1. Yadav, D., et al. AAPS PharmSciTech. 2023, 24, 7. doi.org/10.1208/s12249-022-02467-72. Boczar, D., et al. Pharmaceutics 2022, 14, 1389. doi.org/10.3390/pharmaceutics140713893- Basiglio B, Fumarola M, Longhi M, Zoppi A. ?Desarrollo y caracterización de complejos de inclusión de efavirenz y α-ciclodextrinas?. COIFFA, 2022.