With the aim of the development an ibuprofen (IBU)-loaded NLC with a 2(3) full factorial design, lipid screening and contact angle measurements were applied to choose the most suitable excipients for the formulation of the system. The results of DSC, XRD and FT-IR studies demonstrated the compatibility between the drug and the components. The factorial design was utilized to investigate the effects of the excipients on the zeta potential (ZP) and the mean particle size. The addition of a liquid lipid to the solid lipid decreased both the melting point and the crystallinity index, which also occurred after the dissolution of IBU in the lipid mixture. The XRD diffractograms confirmed the reduction in the crystallinity of the components, but despite this decrease they still retained a crystalline structure. FT-IR did not reveal any interaction between the drug and the excipients. The particle sizes were 129-160 nm, the PDIs ranged between 0.065 and 0.237, and their ZPs varied from -15.40 to -7.54 mV. Random samples (picked out from the design space) were also prepared. Analysis of their particle sizes and ZPs led to an optimum equation which demonstrated the appropriateness of the analysis and allowed the shortening of further experimental planning. (C) 2015 The Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.