Simple Strategy to Protect Lactase Activity in Solid Formulation.

BACKGROUND: Lactose intolerance is characterized by the absence of the enzyme lactase (beta-galactosidase) and affects two thirds of the world adult population. Our aim was to evaluate a lactase gastro-resistant formulation to ensure increased activity in the action site of the enzyme (lumen of the small intestine). Simultaneously, we also evaluated the commercial product stability and enzyme activity, because the product containing beta-galactosidase is classified as food supplement according to the Food and Drug Administration (FDA), so it is free to pass quality testing, efficacy and stability. So, it is possible that contain some irregularities as to the content and enzymatic activity. METHODS: The dissolution assay was performed using a dissolution test system and commercial product and the gastro-resistant formulation were evaluated according to a method adapted to the conditions recommended by United States Pharmacopeia (US Pharmacopeia) for gastro-resistant formulations. For the assessment of enzymatic activity throughout the dissolution test was employed the official method of lactase assay described in US Pharmacopoeia. This method is based on a colorimetric reaction which the substrate reacts with the enzyme generate a colored product further analyzed by UVVisible spectrophotometry. RESULTS: When carrying out dissolution test in commercial product it is noted that the existing formulation is not able to protect the enzyme from degrading action of gastric environment (a loss of 86.0 ± 0.8% of lactase activity was observed). Our proposed gastro-resistant pharmaceutical form there was no loss of activity during the acid step and the end of the dissolution test the found activity was 95 ± 1.3%. CONCLUSION: 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.

Evaluation of skin absorption of drugs from topical and transdermal formulations

ABSTRACT 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.

In vitro evaluation of transdermal nicotine delivery systems commercially available in Brazil

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.

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.