Influência da adição de um insumo nanoestruturado comercial em formulações semissólidas contendo tretinoína : caracterização e estudo da permeação / retenção cutânea

O objetivo deste trabalho foi avaliar as características físico-químicas de um insumo nanoestruturado comercial (IN) e de formulações semissólidas de creme e de gel contendo insumo nanoestruturado e/ou tretinoína, bem como estudar in vitro sua influência na permeação e penetração/retenção cutânea da tretinoína (TTN) a partir de formulações semissólidas. A caracterização abrangeu análises de pH, diâmetro de partícula, fenômenos de instabilidade, potencial zeta e reologia. O estudo de permeação foi conduzido por células de difusão de Franz e da penetração cutânea pelas técnicas de tape stripping e retenção cutânea. O insumo nanoestruturado (IN) analisado consistiu de uma dispersão líquida de aparência opaca e leitosa, com comportamento reológico do tipo newtoniano, pH médio de 6,2±0,05 e potencial zeta de -9,55±1,16 mV. As partículas esféricas presentes na dispersão apresentaram diâmetro de partícula médio de 144±14 nm e baixo índice de polidispersão. As formulações semissólidas apresentaram-se com pH adequado para aplicação cutânea, com teor de TTN próximo ao teórico. A presença no IN não alterou o comportamento reológico das mesmas, mas reduziu o índice de cosnsistência dos géis. As formulações de creme apresentaram uma leve tendência a cremagem. Através de microscopia eletrônica de transmissão verificou-se nanopartículas esféricas e homogêneas com diâmetro em torno de 150 nm para as formulações de creme e gel. No estudo de permeação in vitro não foi detectada a presença de TTN no meio receptor para as diferentes formulações semissólidas. A presença do IN na formulação de creme contendo TTN promoveu uma distribuição mais homogênea do fármaco no estrato córneo (EC). O fluxo da TTN foi reduzido nas camadas adjacentes ao EC a partir de todas as formulações semissólidas. O estudo in vitro de liberação permitiu corroborar maior cedência da TTN pelo gel em relação ao creme, e confirmar uma distribuição mais homogênea/constante do fármaco a partir da base de creme contendo IN. O conjunto dos resultados permitiu concluir que é possível associar tretinoína livre em formulações contendo nanopartículas sem que haja favorecimento da permeação cutânea, mas que podem favorecer a maior homogeneidade de sua distribuição através do estrato córneo.The aim of this work was to evaluate the physicochemical characteristics of the commercial nanostructured ingredient (NI) and semisolids formulations of cream and gel contained nanostructured ingredient and/or tretinoin, as well as to study in vitro its influence on the skin permeation and penetration/retention profile of the tretinoin (TTN) from the semisolids formulations. The characterization analyzes included of pH, diameter of particle, instability phenomena, zeta potential and rheology. The permeation study was conducted by Franz diffusion cells and the study of skin penetration by tape stripping and cutaneous retention techniques. The commercial nanostructured ingredient (NI) consisted of a opaque liquid dispersion with a milky appearance, with newtonian rheological behavior, mean pH of 6.2±0.05, and zeta potential of -9.55±1.16 mV. IN presented spherical particles with mean diameter size of 144 nm and low polidispersion index. The semi-solid formulations showed with pH adequate for cutaneous application and tretinoin content close theorical. The NI presence did not affect the rheological behavior of semi-solid formulations, but decreased the consistency index of gels. The cream formulations presented slight tendency to creaming. Through transmission electron microscopy verified homogeneous and spherical nanoparticles with diameter of particles around 150 nm for the gel and cream formulations. In vitro skin permeation study was not detected the presence of TTN in the receptor compartment. The presence of NI in cream formulation containing TTN promoted a more homogeneous distribution of the drug in the stratum corneum (SC). The flow of TTN was reduced in layers adjacent to the SC from all formulations semissólidas. The in vitro release study corroborate allowed higher yield of TTN by gel compared to the cream, and confirm a more homogeneous distribution/constant of the drug from the cream base containing NI. The set results indicated that it is possible to mix up free-tretinoin in formulations containing nanoparticles without any favoring permeation, but may encourage greater uniformity of their distribution across the stratum corneum

Liquid chromatography method to assay tretinoin in skin layers : validation and application in skin penetration/retention studies

A 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 1; 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 1 (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 1 and 0.0495 μg mL 1, 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

A Radical-Free Approach to Teeth Whitening

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