Solid lipid nanoparticles (SLNs) are a well-tolerated lipid carrier system due to the employment of a physiological and/or biodegradable lipid matrix. Physicochemical properties such as particle size, polydispersity index (PI) and zeta potential are SLN quality response parameters. Increased particle size is a good indicator of in-vitro instability. This work focuses on the importance of selecting the lipid matrices and excipients that can achieve the particle size and stability required if such formulations are to be utilised in the pharmaceutical market. With the aim of understanding the influence of variation in SLN composition (lipid and emulsifier concentration), a Taguchi model of experimental design was applied. Tested factors included the concentration of lipid (stearic acid) and the concentration of Tween®20. SLNs were successfully prepared by a microemulsion-based technique. Based on the hydrophilic lipophilic balance (HLB), different combinations of emulsifiers/co-emulsifiers (Tween®20/Span®20, Tween®20/Span®80, Tween®20/n-butanol, and Tween®20/iso-propanol) were also used to control the physicochemical properties of SLNs. The influence of pH (addition of HCl or NaOH) and electrolyte (addition of NaCl), both during and after the preparation, were also investigated on selected SLN formulations. Slightly polydispersed (PI < 0.3) nanoparticles with a particle size < 450 nm and zeta potential range of +5 to –50 mV were developed. Physical stability of optimised stearic-acid based SLNs over 2 months were assessed by particle size measurement. SLNs were stable when refrigerated. These results suggest that thoughtful selection of lipid and lipid excipients is essential for successful preparation and physical stability of SLNs. This study facilitates the preliminary physicochemical characterisation for favourable encapsulation of lipophilic and hydrophilic drugs.