Pharmacokinetics and In Vitro and In Vivo Correlation of NNdimethylaminocurcumin (NNDMAC) Loaded Polycaprolactone Microspheres in Rats

NN-dimethylaminocurcumin (NNDMAC), a novel curcumin analogue, has demonstrated significant hepatoprotective activity after oral administration. The objective of this investigation was to determine the pharmacokinetics of NNDMAC after the administration of its microsphere formulation. Additionally, it was aimed to determine the in vitro in vivo correlation (IVIVC) with the microsphere formulation. NNDMAC biodegradable microspheres were prepared using solvent evaporation technique by taking polycaprolactone as the polymer. A suitable release study based on the volume of distribution of NNDMAC was selected. In vitro release of the drug was determined. For in vivo studies, the microsphere formulation was injected by IP route. Pharmacokinetic properties of microsphere-encapsulated NNDMAC were determined and a comparison with i.v. solution form of NNDMAC was made. Pharmacokinetic analysis was performed using KINETICA and non-compartmental parameters were determined. Concentrations of the drug in plasma were determined by HPLC. IVIVC was established according to Drewe and Guitard (degree A). In vivo drug release into the systemic circulation was determined using Wagner-Nelson method. Results indicated that, when NNDMAC formulations were administered by IP route, mean residence time (MRT) and the area under the curve (AUC) were significantly higher (P<0.05) and maximum concentration (C_max) of NNDMAC was lower than that of the free form. T was same with both the administrations. The max results obtained in the present study showed that microsphere encapsulated NNDMAC provides prolonged and effective plasma concentration after IP administration. The microsphere formulation sustained the release of the active for 9 days in vitro as well as in vivo in this rat model. Good IVIVC was achieved when the release medium selected was based on the volume of distribution of the drug.