Preformulation Studies and Bioavailability Enhancement of Curcumin with a 'Two in One' PEG-ß-Cyclodextrin Polymer.

ABSTRACT

Drug delivery systems are used to improve the biopharmaceutical properties of curcumin. Our aim was to investigate the effect of a water-soluble 'two in one' polymer containing covalently bonded PEG and ßCD moieties (ßCPCD) on the solubility and bioavailability of curcumin and compare it to a polymeric ß-cyclodextrin (ßCDP) cross-linked with epichlorohydrin. Phase-solubility and dynamic light scattering (DLS) experiments showed that the solubility of curcumin increased significantly in 10 m/m % ßCPCD and ßCDP solutions, but ßCPCD-curcumin particles had higher hydrodynamic volume. The formation of the ßCPCD-curcumin complex in solution and sedimented phase was confirmed by NMR spectroscopy. Biocompatibility and permeability experiments were performed on Caco-2 cells. Polymers did not show cytotoxicity up to 10 m/m % and ßCPCD significantly increased the permeability of curcumin. DLS measurements revealed that among the interaction of polymers with mucin, ßCPCD formed bigger aggregates compared to ßCDP. Curcumin complexes were lyophilized into capsules and structurally characterized by micro-CT spectroscopy. Drug release was tested in a pH 1.2 medium. Lyophilized complexes had a solid porous matrix and both ßCPCD and ßCDP showed rapid drug release. ßCPCD provides an opportunity to create a swellable, mucoadhesive matrix system for oral drug delivery.