Background: Traditional bleaching agents based on hydrogen peroxide (HP) or carbamide peroxide (CP) have adverse soft and hard tissue effects. Objectives: This study tested a novel formulation of phthalimidoperoxycaproic acid (PAP) with additives to optimise its safety and effectiveness. Methods: A novel gel (PAP+) was formulated. Laboratory studies assessed effects of six 10-minute exposures to PAP+ vs. commercial CP and HP gels, using surface profilometry and microhardness. The effectiveness of PAP+ in vitro against complex polyphenol stains on enamel was compared to 6% HP. Results: Unlike HP gels, PAP+ gel did not erode enamel. Unlike both CP and HP gels, PAP+ gel did not reduce the surface microhardness of enamel. PAP+ gel on used on polyphenol stains was superior to 6% HP. In this model, six repeated 10-minute treatments with PAP+ gel could improve the shade by approximately eight VITA® Bleachedguide shades. Conclusions: These laboratory results support the safety and effectiveness of this new PAP formula and its use as an alternative to CP and HP with superior safety and effectiveness.

A B S T R A C TA liquid chromatography (LC) method for the quantification of tretinoin (TTN) in different matrices (adhesive tape, cotton and porcine skin layers, stratum corneum, viable epidermis, and dermis) was validated and applied in in vitro porcine skin penetration/retention studies. This study proposes, for the first time, a method for assaying TTN in separated porcine skin layers (stratum corneum, viable epidermis, and dermis). The skin studies were carried out using tape stripping and cutaneous retention techniques. The procedures for the extraction of TTN from dermatological formulations (creams and gels) and biological and non-biological matrices used with the tape stripping and retention techniques were also evaluated. The LC method consisted of a mobile phase composed of a mixture of methanol, water, and glacial acetic acid (85:15:1, v/v); a C18 column used as the stationary phase; a flow rate of 1.0 mL min À1 ; an injection volume of 100 μL; and TTN detection at 342 nm. The method was linear in the range of 0.05-15.00 μg mL À1 (r ¼ 0.9999), and it was precise and accurate. The limit of detection (LOD) and limit of quantification (LOQ) were 0.0165 μg mL À1 and 0.0495 μg mL À1 , respectively. TTN was extracted from different matrices, showing good precision [relative standard deviation (RSD) of <5%] and accuracy (89.4-113.9%). This method was successfully applied in the evaluation of TTN skin retention/permeation from dermatological formulations (cream and gel). A higher penetration of TTN through the skin was achieved with the gel rather than the cream, showing the influence of the dosage form. Therefore, the developed method can easily be applied in porcine skin penetration/retention studies of dermatological formulations containing TTN, and it is able to discriminate the behaviours of the different formulations.