Comparative In vivo Evaluation of Aripiprazole Coprecipitate, Nanoparticles and Marketed Tablets in Healthy Human Volunteers and In vitro-In vivo Correlation

The aim of this study was to evaluate the bioavailability of two aripiprazole tablets, coprecipitate (CP) and nanoparticles (NP) when compared to the market tablets. A single-dose, randomized, three period crossover design under fasting conditions in healthy human volunteers was studied. The dissolution rate of the CP, NP and market tablets was determined. In order to investigate the feasibility of in vitro data as a tool for predicting in vivo results, two types of in vitro-in vivo correlation (IVIVC), level C and multiple level C, were studied. Almost 75% of aripiprazole was dissolved from the nanoparticles tablets within 10 minutes compared with 20% and 46% for coprecipitate and market tablets, respectively. The mean AUC_0–72value of aripiprazole from the NP tablets (6136.35 ± 421.29 ng.hr/mL) was significantly higher than both CP tablets (3216.12 ± 525.02 ng.hr/mL) and market tablets (5215.57 ± 457.28 ng.hr/mL) (p d” 0.05). The relative bioavailability of aripiprazole after oral administration of the CP and NP tablets was 61.66% and 117.65%, respectively. The higher dissolution rate of NP tablets resulted in rapid absorption of aripiprazole and consequently higher bioavailability. Multiple level C IVIVC showed the bioequivalence of NP andbioinequivalence of the CP tablets in comparison to market tablets.