Περίληψη:
Hydrophobic matrices were prepared using Eudragit RS 100, flurbiprofen (as a model drug), with sorbitol as a diluent and magnesium stearate as a lubricant. The effect of adding each of five surface active agents (sodium lauryl sulphate, sodium taurocholate, cetylpyridinium chloride, cocamidopropyl betaine and cetrimide) individually to the matrix was investigated. To explore the mechanism by which the rate of drug release was increased following the incorporation of surfactants, experiments were undertaken to assess the wettability of the different formulations, and to measure drug release in the presence of submicellar and micellar concentrations of the surfactants. The results were also compared to those which have been reported previously for Eudragit RL based matrix formulations. Three mechanisms were proposed by which drug release could be increased following the addition of surfactants: improved wetting, solubilisation, and the dissolution of the soluble surfactants to form disruptions in the matrix. Only sodium taurocholate and sodium lauryl sulphate showed any significant increase in dissolution rate. From contact angle measurements, these were found to be the only two surfactants which increased the wettability of the tablets. Thus it was concluded that increased wettability is a prerequisite to an increase in dissolution rate. The increase in dissolution rates in the presence of surfactant solutions was, however, very small compared to the increase observed when the surfactant was incorporated within the matrix itself. By comparison with data for release from RL matrices, it is likely that the increase in dissolution rate when the surfactant is present in the matrix is related to the solubility of the surfactant. Thus it is necessary for the surfactant to increase the wettability of the tablet surface, to allow the fluid to gain access to the hydrophobic matrix, and then to dissolve. The increased dissolution rate is probably due to either the formation of pores due to the dissolution of the surfactant, or more likely, because of the influence of high local concentrations of surfactant solution, perhaps affecting adhesion within the matrix, leading to disintegration and thus dissolution. The charge of the surfactant also produced a significant effect. The anionic surfactants resulted in lowering of contact angles and increased dissolution rates; the cationic surfactants did not result in changes in contact angle and caused smaller changes in dissolution. It is probable that there is an interaction between the cationic surfactants and the anionic model drug, resulting in an inactivation of these surfactants. Anionic/cationic interactions are not unexpected, but the presence of such an observation for this system (based on Eudragit RS) is surprising because no such interactions were observed for similar formulations based on Eudragit RL (published previously) (Eudragit RL and RS differ only in the extent of the quaternary ammonium substitution; RS being much greater than RL). © 1991.
Συγγραφείς:
Buckton, G.
Efentakis, M.
Al-Hmoud, H.
Rajan, Z.
