Preparation and characterization of dry β-cyclodextrin-based ternary complexes of haloperidol and lactic acid for drug delivery

Abstract

This study was aimed to prepare dry β-cyclodextrin (β-CD)-based ternary complexes of haloperidol (HALO) with lactic acid for drug delivery. The influences of different media (buffers pH 3 and pH 6) and preparation methods ((freeze drying (FD) and solvent evaporation (SE)) on the HALO inclusion complexes were determined. HALO/β-CD/lactic acid ternary complexes prepared in buffer pH 3 exhibited higher inclusion yield than those in buffer pH 6. Furthermore, HALO/β-CD/lactic acid ternary complexes prepared via FD gave higher inclusion yield than those prepared via SE. The physicochemical properties of dry HALO/β-CD/lactic acid ternary complexes prepared in buffer pH 3 were subsequently determined. The interaction of HALO, β-CD and lactic acid was found and confirmed by Fourier transform infrared and proton nuclear magnetic resonance. Results from differential scanning calorimetry and X-ray powder diffractometry depicted that the β-CD ternary complexes of HALO and lactic acid prepared via FD in buffer pH 3 transformed the drug from a crystalline state to an amorphous state. With significantly enhanced release of HALO from the complexes, HALO/β-CD/lactic acid ternary complexes was shown to be a promising carrier for HALO delivery.