The skin barrier function has been attributed to the stratum corneum and represents a major challenge in clinical practice pertaining to cutaneous administration of drugs. Despite this, a large number of bioactive compounds have been successfully administered via cutaneous administration because of advances in the design of topical and transdermal formulations. In vitro and in vivo evaluations of these novel drug delivery systems are necessary to characterize their quality and efficacy. This review covers the most well-known methods for assessing the cutaneous absorption of drugs as an auxiliary tool for pharmaceutical formulation scientists in the design of drug delivery systems. In vitro methods as skin permeation assays using Franz-type diffusion cells, cutaneous retention and tape-stripping methods to study the cutaneous penetration of drugs, and in vivo evaluations as pre-clinical pharmacokinetic studies in animal models are discussed. Alternative approaches to cutaneous microdialysis are also covered. Recent advances in research on skin absorption of drugs and the effect of skin absorption enhancers, as investigated using confocal laser scanning microscopy, Raman confocal microscopy, and attenuated total reflectance Fourier-transform infrared spectroscopy, are reviewed. Uniterms:Skin absorption/effects/study. Skin absorption/topical formulations. Skin absorption/ transdermal formulations. Skin absorptions/enhancers. INTRODUCTIONTopical and transdermal drug delivery systems have shown significant advantages in clinical practice for drug targeting to the action site in the body; this has reduced the systemic side effects. The administration of drugs by through the skin is also performed to achieve controlled or prolonged drug delivery, and this route can be explored as an alternative to the oral route. The oral route shows some limitations for drugs with irregular absorption in the gastrointestinal tract and low bioavailability and for drugs with increased first pass metabolism and short plasma halflife times (Barry, 2001;Wokovich et al., 2006;Prausnitz, Langer, 2009;Alexander et al., 2012).Many drug products applied to the skin surface may penetrate to some extent into the skin layers, where their effects are expected. This is the case for topical formulations for treatment of skin disorders such as acne and cutaneous inflammatory diseases that include dermatitis, erythematous lupus, and psoriasis. On the other hand, transdermal formulations release drugs that permeate through the skin and enter the systemic circulation. Transdermal therapy must ensure that significant concentrations of the drug are absorbed to reach effective plasma concentrations. Permeation of drugs is targeted in some cases to body regions close to the action site, where a regional effect is expected, e.g., in the muscles, blood vessels, and articulations. In this way, the term "cutaneous absorption" is properly used to characterize the sum of the amounts of drug that penetrate and permeate the skin (Barry, 2001;El Maghraby, Barry;Willi...

The aim of this study was to develop and validate a method for evaluating the release and skin permeation from transdermal nicotine patches using the vertical diffusion cell (VDC). The VDC is an experimental apparatus employed in research, development, and the pharmaceutical field because it can simulate conditions closest to those established in clinical trials. Two transdermal nicotine delivery systems marketed in Brazil to release 14 mg over 24 hours were evaluated. Release studies were carried out using a regenerated cellulose dialysis membrane and permeation studies were carried out using excised porcine ear skin. The results indicated that nicotine release from both evaluated patches follows Higuchi's release kinetics, while skin permeation studies indicated zero-order release kinetics. Nicotine release rates were different between both evaluated patches, but drug permeation rates were not significantly different. According to validation studies, the method was appropriate for evaluating in vitro performance of nicotine patches. The proposed method can be applied to in vitro comparative studies between different commercial nicotine patches and may be used as an auxiliary tool in the design of new transdermal nicotine delivery systems.Uniterms: Nicotine/release and skin permeation. Transdermal delivery patches/evaluation. Vertical diffusion cell. Skin permeation. Transdermal formulations/ nicotine delivery systems.O objetivo deste trabalho foi o desenvolvimento e a validação de metodologia empregando a célula de difusão vertical para avaliação da liberação e permeação cutânea in vitro de nicotina a partir de adesivos transdérmicos. A célula de difusão vertical é considerada um aparato experimental importante em pesquisa e desenvolvimento e pode simular condições in vitro próximas aquelas observadas em ensaios clínicos. Neste trabalho foram avaliados dois dispositivos transdérmicos comercializados no Brasil para liberação controlada de 14 mg de nicotina em um período de 24 horas. Realizaram-se ensaios de liberação, usando membranas de diálise de celulose regenerada, e estudos de permeação cutânea, usando pele de orelha de porcos. Os resultados indicaram que a liberação da nicotina em ambos os dispositivos transdérmicos avaliados seguiu a cinética de Higuchi, enquanto que a permeação cutânea seguiu cinética de ordem zero. As velocidades de liberação foram diferentes para os dispositivos comerciais avaliados, entretanto não foram encontradas diferenças significativas para as velocidades de permeação cutânea. Conforme os estudos de validação, a metodologia mostrou-se apropriada para a avaliação in vitro da liberação e permeação cutânea a partir de adesivos transdérmicos de nicotina. O método proposto foi aplicado em estudos comparativos in vitro entre adesivos transdérmicos comerciais contendo nicotina. Deste modo, o método também pôde ser considerado como ferramenta útil que poderia ser aplicada durante o desenvolvimento de novas formulações transdérmicas para liberação de nicotina.Unitermos: Nicotina/liberaçã...

Darunavir (DAR) is a synthetic antiretroviral drug widely used around the world as an important component of HIV therapy. Usually, DAR is commercialized at ethanolate crystalline form. Under different environmental conditions, different pseudo-polymorphic forms arise and convert each other. The importance of the drug stability control is to ensure their quality, efficacy and safety. Therefore, the aim with this work was to evaluate the solidstate stability of DAR under stressed conditions and assess the role played by the formulation and package in providing stability to the drug. In this work, DAR ethanolate raw material and its tablet formulation were stocked under stress condition (55°C) and monitored for 94 days. Thermal analysis (DSC and TG) and powder X-ray diffraction were used to evaluate possible polymorphic changes. There has been alteration of the crystalline structure of the raw material and the tablets stored outside of the primary packaging. However, the tablets kept within the primary package during the entire time remained with intact crystal structure, suggesting that as important as the formulation or coating is the protection provided by the packaging to the product used today. Thus, the packaging material to be used in the product containing DAR should be chosen carefully.

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The formulations proposed in this work using hypromellose capsules ensure the enzymatic activity of lactase, preventing its contact with the acid medium. For the other side, the results of commercial tablets for lactase release indicate a significant loss of enzyme activity due to the immediate release of the enzyme in the simulated gastric fluids.