Ensuring the physical stability of drug nanosuspensions prepared via wet media milling has been a challenge for pharmaceutical scientists. The aim of this study is to assess the combined use of non-ionic cellulosic polymers and anionic surfactants in stabilizing multiple drug nanosuspensions. Particle size of five drugs, i.e. azodicarbonamide (AZD), fenofibrate (FNB), griseofulvin (GF), ibuprofen (IBU) and phenylbutazone (PB) was reduced separately in an aqueous solution of hydroxypropyl cellulose (HPC) with/without sodium dodecyl sulfate (SDS) via a stirred media mill. Laser diffraction, scanning electron microscopy, thermal analysis, rheometry and electrophoresis were used to evaluate the breakage kinetics, storage stability, electrostatic repulsion and stabilizer adsorption. Without SDS, drug particles exhibited aggregation to different extents; FNB and GF particles aggregated the most due to low zeta potential and insufficient steric stabilization. Although aggregation in all milled suspensions was reduced due to HPC-SDS combination, FNB and IBU showed notable growth during 7-day storage. It is concluded that the combination of non-ionic cellulosic polymers and anionic surfactants is generally viable for ensuring the physical stability of wet-milled drug nanosuspensions, provided that the surfactant concentration is optimized to mitigate the Ostwald ripening, whereas cellulosic polymers alone may provide stability for some drug suspensions.
Keywords: Aggregation; Ostwald ripening; bioavailability enhancement; drug nanoparticles; physical stability; wet media milling.