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Research Article

Is the combination of cellulosic polymers and anionic surfactants a good strategy for ensuring physical stability of BCS Class II drug nanosuspensions?

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Pages 499-510 | Received 08 Dec 2014, Accepted 17 Feb 2015, Published online: 16 Mar 2015
 

Abstract

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.

Declaration of interest

The authors report financial support through Grant EEC-0540855 from the U.S. National Science Foundation (NSF) Engineering Research Center (ERC) for Structured Organic Particulate Systems (SOPS). Nisso America Inc. is also noted for the kind donation of the HPC samples.

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