AbstractOne of the endless challenges in the pharmaceutical industry is the poor oral bioavailability of drugs associated with poor solubility. Curcumin, a yellow-orange substance that is extracted from the spice turmeric (Curcuma longa, Zinziberaceae), has been attributed with a wide range of pharmacological activities for the prevention and treatment of many diseases. However, its potential for use as an orally delivered medicinal product is hindered by its extremely poor aqueous solubility and oral bioavailability. Many techniques have been applied to overcome the bioavailability problem of curcumin and solid dispersions were reported to be one of the most promising strategies to improve the solubility, dissolution rate and bioavailability of curcumin.
The objective of this study was to develop novel polymer-surfactant-based solid dispersion formulations for curcumin to increase its aqueous solubility and potentially increase oral bioavailability. Through a series of screening processes, a curcumin + Soluplus + Vitamin E TPGs (1:10:10) solid dispersion prepared by solvent evaporation + freeze-drying method was selected as the novel curcumin solid dispersion formulation, and it was named “Solucumin”. It has significantly increased the solubility of curcumin, with solubility study results showing the curcumin solubility 582-fold and 937-fold higher than commercial grade curcumin in pH 1.2 and 6.8 aqueous solutions, respectively. In vitro dissolution study, in vitro Caco-2 cell permeability and uptake studies and characterisation studies (FTIR, DSC, XRD, DLS, Zeta-potential and a short-term physical stability test) were conducted for Solucumin and it was compared with two marketed curcumin products (Longvida® and Nacumin®) and a polymer-surfactant-based solid formulation of curcumin (Mexcumin).
Solucumin has exhibited significantly higher dissolution, cellular improving the dissolution of other curcuminoids (demethoxycurcumin and bisdemethoxycurcumin) compared with Mexcumin. XRD and DLS confirmed the amorphisation of curcumin and particle size reduction in Solucumin, which could be the main reasons for the improved curcumin solubility and dissolution. FTIR showed no curcumin in Solucumin was adhered to the surface of the excipients. DSC revealed that Vitamin E TPGs in Solucumin melted at human body temperature (37ºC) and it could dissolve curcumin. In the short-term stability test, Solucumin showed it has a degradation-resistant effect for at least a month.
In addition to curcumin, Solucumin technology has also been tested on other poorly water-soluble drugs/natural compounds to investigate its effect on drug/compound dissolution. It was found that Solucumin has significantly improved the dissolution of niclosamide, nitrofurantoin, terbinafine, quinine and quercetin in a pH 6.8 dissolution medium.
Overall, it can be concluded that Solucumin, the novel solid dispersion formulation developed in this study, succeeded in significantly improving the aqueous solubility, dissolution and permeability of curcumin. It is a promising formulation for improving the oral bioavailability not only of curcumin but also of other drugs/natural compounds with poor water solubility.
|Date of Award||Dec 2022|
|Supervisor||Ananth Pannala (Supervisor) & John Smart (Supervisor)|