Moreover, the combining of glycine isopropyl ester and L-proline alkyl esters with (_S_)-naproxen has been found to be the highest beneficial for a significant increase in drug permeability through pig skin compared to the free acid form of (_S_)-naproxen [12; 13]. In addition to appropriate selection of active compound form, searching for formulations and appropriate compositions is advisable to ensure better release and penetration of naproxen. Selecting the appropriate vehicle can increase penetration and obtain an immediate therapeutic effect. Microemulsion formulations based on isopropyl myristate in oil phase and different surfactants increased the topical delivery of naproxen [7]. Topical gel formulations with naproxen sodium were also developed using a different type of gel forming agents that revealed a better release and permeation of naproxen with a decrease in concentration of gel forming agent with inclusion of certain enhancers [8; 10]. In recent years, various carriers with specific compositions have been proposed to increase drug permeation. One such vehicle is Pentravan(r), an oil-in-water (o/w) emulsion base. Despite the relatively high water content, this medium has the consistency of a thick, yellowish cream with a pH of 4.0-5.5. The composition of this vehicle includes components that facilitate the permeation of the drug through the skin, improve its hydration, and preserve, stabilize, and improve the rheology of ointments and creams [2]. Pentravan(r) is a registered pharmaceutical raw material, comprising ingredients approved by regulatory agenciesfor pharmaceutical uses worldwide. It is used as a vehicle in topical skin compositions on prescription that are made in compounding pharmacies. Prescription analgesic and anti-inflammatory drug topical compositions are developed by physicians to individualize pharmacotherapy for patients with pain of various origins, primarily chronic, e.g., in musculoskeletal and rheumatic diseases and soft tissue pain. Selecting the appropriate form of the active substance as the best possible carrier and excipient in topically administered NSAIDs plays a crucial role in the increase of drug permeation and allows for improved analgesia and anti-inflammatory effects. In our previous studies, we have shown that Pentravan(r) is an excellent vehicle for (S)-naproxenate of L-prolinium isopropyl ester [ProGiPr][NAP]. The cumulative mass of permeated naproxen from this composition through the model STRAT-M(r) membrane was statistically several times higher than for both the acid naproxen incorporated into the same vehicle and commercially available topical gels with either the acid form of naproxen or the sodium salt form [13]. Considering that the penetration of the active ingredient may be modulated by the specific ingredients of topical compositions, our efforts in the presented studies were focused on the effect of penetration enhancers from the group of sensates as menthol and capsaicin on the naproxen permeation. Moreover, menthol or capsaicin have analgesic effects confirmed in experimental and clinical models. Our studies are crucial for the development of topical compositions used in individual pain pharmacotherapy using physicians' own recipes made in compounding pharmacies. In the presented studies, in vitro permeation tests were performed in Franz diffusion cells using human skin, instead of the artificial STRAT-M(r) membrane which was used in our previous studies [13]. Human skin penetration studies are necessary to progress to clinical trials. Additionally, the stability of prepared compositions and their rheological properties were assessed.