Supersaturation is a very useful method of enhancing the permeation of drugs across membranes such as skin, because unlike other methods, it does not interfere with the ultrastructure of the stratum corneum. Many drugs are able to form inclusion complexes with β-cyclodextrins (β-CDs) and this study investigates the anti-nucleating effects of these compounds on supersaturated solutions of diclofenac. The ability of various βCDs to form inclusion complexes with diclofenac was assessed by measuring their saturated solubilities. Solutions containing hydroxypropyl β-cyclodextrin (HPβ-CD, with a molar substitution of 0.9) produced a 7.5-fold increase in the solubility of diclofenac, which suggested that a strong complex was formed between the two compounds. This association was characterized using differential scanning calorimetry. Permeation across silicone membranes of these saturated solutions of diclofenac in the presence of the different βCDs produced similar flux values suggesting that the overall activity was also similar. The effect of different molar ratios of HPβ-CD and diclofenac, and the anti-nucleating effect of HPβ-CD (both on its own and in combination with a known anti-nucleant, hydroxypropylmethyl cellulose (HPMC)) on the diffusion of diclofenac across silicone membranes was investigated. HPβ-CD appears to have a stabilizing effect on supersaturated solutions of diclofenac as a co-ingredient with HPMC.