Formulation strategies to improve the solubility and ex vivo membrane permeability of curcumin

Abstract

The natural compound known as curcumin has pharmacological activities including antiinflammatory and antioxidant effects. Unfortunately, the aqueous solubility, membrane permeability and bioavailability of curcumin is very low due to its lipophilic characteristics. Curcumin is also rapidly eliminated in the body that results in limited therapeutic effects. The main goal of this study was to increase the solubility of curcumin and thereby its membrane permeability by using two different formulation strategies, which included formulation of an inclusion complex with hydroxypropyl-β-cyclodextrin as well as amorphous solid dispersions with different polymers (PVP 30 and HPMCAS). The formulations were characterised by means of Fourier-Transform infrared spectroscopy, X-ray powder diffraction, simultaneous thermal gravimetric analysis and polarised light microscopy. Solubility studies were conducted on the formulations and a significant increase in the solubility of curcumin (p < 0.05) was achieved with the formulations. The solubility studies resulted in a 1.89-fold, 19.70-fold and 0.47-fold increase for curcumin when applied as the HPβCD inclusion complex and as ASDs with PVP 30 and HPMCAS, respectively. Dissolution studies revealed a noticeable improvement in the rate and extent of dissolution of curcumin in the formulations compared to that of pure curcumin. A significant difference in the dissolution concentrations were obtained with the formulated HPβCD inclusion complex as well as the formulated ASDs with PVP 30 (p < 0.05). The peak concentration of pure curcumin obtained at 15 min during the dissolution test was increased from 2.465 ug/mL to 58.801 ug/mL at 120 min, when applied as the HPβCD inclusion complex and also increased to 71.646 ug/mL at 60 min when applied as the ASD with PVP 30. The formulated ASD with HPMCAS displayed a significant decrease (p < 0.05) at the end of 120 min. Although curcumin permeation was very low in general, the ex vivo permeation results showed a definitive increase in membrane permeability of curcumin in the formulations as compared to curcumin alone, which was statistically significant for the PVP 30 ASD formulation. A significant increase in the percentage curcumin entrapment in the intestinal epithelial tissue was also observed when curcumin was applied as the formulated ASD with PVP 30 (p < 0.05). Additional research will have to be conducted to improve the movement of the entrapped curcumin molecules from the tissue to the basolateral side in order to increase its absorption and thereby also its bioavailability.