This study aimed to evaluate and compare, using the methodology of Franz diffusion cells, the ketoprofen (KTP) releasing profiles of two formulations: A gel and a conventional suspension. The second aim was to show that this methodology might be easily applied for the development of semi-solid prototypes and claim proof in pre-formulation stages. Drug release analysis was carried out under physiological conditions (pH: 5.6 to 7.4; ionic strength 0.15 M; at 37 °C) for 24 h. Three independent vertical Franz cells were used with a nominal volume of the acceptor compartment of 125 mL and a diffusion area of 2.5 cm2. Additionally, two different membranes were evaluated: A generic type (regenerated cellulose) and a transdermal simulation type (Strat-M®). The KTP permeation profiles demonstrated that depending on the membrane type and the vehicle used, the permeation is strongly affected. High permeation efficiencies were obtained for the gel formulation, and the opposite effect was observed for the suspension formulation. Moreover, the permeation studies using Strat-M membranes represent a reproducible methodology, which is easy to implement for pre-formulation stage or performance evaluation of semi-solid pharmaceutical products for topical or transdermal administration.