DEVELOPMENT AND CHARACTERIZATION OF CO-GROUND MIXTURES AND SOLID DISPERSIONS OF ARIPIPRAZOLE WITH HYDROPHILIC CARRIERS

Objective: The aim of the present work was to improve the dissolution of poorly water-soluble drug Aripiprazole (ARP) and to understand the effect hydrophilic carriers [guar gum(GG), modified guar gum (MGG), and hydroxypropyl methylcellulose (HPMC)]on drug solubility. Methods: Physical Mixture (PM), ground mixtures (GM) and solid dispersions (SD) were prepared by simple mixing, metal ball mill (MBM) and solvent evaporation method, respectively. Results: The solubility of ARP in simulated gastric fluid and simulated intestinal fluid at 370 C was found to be 76.78 μg/mL and 291μg/mL, respectively. Grinding time affects the dissolution rate was observed. Ground mixture develops more fine particles and show less friability index than physical mixture and solid dispersion. FTIR studies reveals no chemical interaction between drug and carriers. The carriers showed the wettability of the ground products in the order MGG > GG >HPMC. The order of dissolution rate enhancement of the different hydrophilic carriers was in the order of MGG>GG>HPMC. GM containing MGM showed better dissolution than SD and PM. Conclusion: From the study it was concluded that grinded ARP with hydrophilic carriers improved the dissolution rate not only due to particle size reduction, but also resulted from the ability of these carriers to prevent aggregation of the finely divided drug particles, to improve wettability and to inhibit recrystallization during dissolution.