Optimization of a drug simultaneous dissolution and permeability screening method

• Autor(a) principal: Ferreira, Pedro
• Data de Publicação: 2008
• Outros Autores: Serra, Hugo, Pedro, João Mário, Graça, Anabela, Simplício, Ana Luísa
• Tipo de documento: Artigo
• Idioma: por
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: https://doi.org/10.25758/set.144
• topic: Biodisponibilidade; Dissolução; Permeabilidade; Métodos in vitro; Bioavailability; Dissolution; Permeability; In vitro methods

The goal of this research project was the optimization of a method for simultaneously screening the dissolution rate and the permeability of drug formulations across Polyvinylidene Fluoride membranes, using a bilateral flow cell. Initially, the effect of several variables was tested on caffeine and acetylsalicylic acid permeability. The obtained results showed that the method is more reproducible when the flow cell is used with the unilateral flow at the donor side and with stirring on the acceptor side. It was also showed that the method is able to detect the influence of pH (caffeine Papp at pH 7,4 and 4,5: 4,84±1,57x10-5cm.s-1 and 6,00±0,70x10-5cm.s-1; acetylsalicylic acid Papp at pH 7,4 and 4,5: 3,85±0,38x10-5cm.s-1 and 5,11±0,65x10-5cm.s-1) and excipients (Papp of isolated caffeine and in the presence of excipients: 6,76±1,22x10-5cm.s-1 and 5,84±0,43x10-5cm.s-1; Papp of isolated acetylsalicylic acid and in the presence of excipients: 7,07±1,56 x 10-5cm.s-1 and 5,19±0,23x10-5cm.s-1) in drug permeability. A dissolution medium with pH 4.5, defined in the United States Pharmacopeia (USP) for caffeine/acetylsalicylic acid tablets, was used. Another biorelevant method was developed using a dissolution media with pH 7.4 due to the future goal of testing drug permeability with Caco-2 cellular membranes. The dissolution percentages with this new media were 96,3% for caffeine and 87,1% for acetylsalicylic acid, higher than the 80% minimum limit described by the USP, making it possible to use this media in all the permeability assays. After the establishment of the isolated dissolution and permeability methodologies, the next step was the connection of both techniques. The dissolution/permeability assays were performed with a commercial pharmaceutical form containing both caffeine and acetylsalicylic acid (Melhoral®). The permeability results were reproducible and allowed discrimination between different media, opening therefore the possibility of its application in future works using cellular (Caco-2) or tissue (skin and intestinal) membranes.