Simultaneous formation of inclusion complex and microparticles containing Albendazole and β-Cyclodextrin by supercritical antisolvent co-precipitation

Abstract

Albendazole (ABZ) is an effective anthelmintic and an anticancer candidate. Due to the low oral bioavailability associated with its poor aqueous solubility, high doses are required, and dose-related side effects are reported. To enhance ABZ dissolution different formulation approaches were proposed, among others, its combination with cyclodextrins. In this work, co-precipitation of β-cyclodextrin and ABZ was performed by supercritical antisolvent technique as an alternative preparation method. The operating temperature and pressure of the experiments were selected by thermodynamic modeling with the purpose of obtaining a miscible solution between solvent mixture (DMSO + acetone) and CO2. Precipitated microparticles were characterized by spectroscopic, thermal, and crystallographic analysis in order to demonstrate the formation of a new solid form. The characterization evidenced that tautomer II of ABZ was obtained by precipitation in supercritical CO2 medium. The change of the crystalline phase was discussed in light of the results reported in the literature. Composite microparticles were obtained with a mean diameter ranging from 0.45 to 1.4 μm. An increase of about 4 times in the ABZ dissolution rate was measured for the particles with a 3:1 ABZ:β-cyclodextrin molar ratio with respect to the corresponding physical mixture and pure ABZ obtained by the same method. The dissolution improvement was attributed to the formation of the inclusion complex and a synergetic effect between both components, rather than the increase obtained for the change of ABZ to polymorphic form II.