The influence of organic solvents on artificial membranes when assessing drug release from topical formulations is, generally, poorly characterised yet current guidelines require no characterisation of the membrane before, during or after an experiment. Therefore, the aim of this study was to determine the effect of solvent-membrane interactions when using in-vitro Franz cell methods for the assessment of corticosteroid release and to assess compliance or otherwise with Higuchi's equation. The rate of beclometasone dipropionate monohydrate (BDP) and betamethasone 17-valerate (BMV) release across a regenerated cellulose membrane (RCM), from both saturated solutions and commercial formulations, was determined. Increasing the ratio of organic solvent, compared with aqueous phase, in the donor fluid (DF) resulted in up to a 416-fold increase in steady-state flux. Further, alterations in the receiver fluid (RF) composition caused, in some cases, 337-fold increases in flux. Analysis indicated that the RCM remained chemically unchanged, that its pore size remained constant and that no drug partitioned into the membrane, regardless of the DF or RF employed. However, it was observed that the organic solvents had a thinning effect on the RCM, resulting in enhanced flux, which was potentially due to the variation in the diffusional path length. Such findings raise issues of the veracity of data produced from any membrane release study involving a comparison of formulations with differing solvent content.