Effect of fixed aqueous layer thickness of polymeric stabilizers on zeta potential and stability of aripiprazole nanosuspensions.

The aim of this study was to evaluate the effect of the thickness of adsorbed polymer layer (also known as Fixed Aqueous Layer Thickness, FALT) of polymeric stabilizers on zeta potential and stability of nanoparticles in a suspension. Aripiprazole, a poorly water soluble drug was used as a model drug to evaluate rationale for increased FALT and to understand the effect of hydrophilicity and hydrophobicity of polymeric stabilizers on FALT of aripiprazole nanosuspensions. The nanosuspensions were prepared by media milling and Pluronic F68, Pluronic F127, Hydroxypropyl methylcellulose (HPMC) and Hydroxypropyl cellulose (HPC) were used as polymeric stabilizers. The particle size (immediately after preparation and after 1 week of storage at 25°C) and zeta potential of aripiprazole nanosuspensions were determined. For Pluronics, FALT was determined theoretically whereas for HPMC and HPC it was calculated as Debye Huckel parameter from the zeta potential dependence on the ionic strength. An increase in FALT resulted in reduced zeta potential. With an increase in FALT of polymers used, the stability of nanosuspensions showed improvement. Furthermore, a linear correlation was shown to exist between the FALT and length of hydrophilic chains in Pluronics.