Investigation of the drug distribution and release characteristics from particulate membranes

Abstract

A new type of membrane structure has been developed for drug delivery that offers a biphasic release behavior. A mixture of DMSO, poly(ethylene-vinyl alcohol) (EVAL) and drug was precipitated from 1-octanol to form membranes by constituent particles bonded to each other. The drug can be distributed between particles or trapped in the particles during membrane formation, thereby allowing control of release kinetics. The drug release profile from the EVAL membrane was investigated using water as a release medium. Doxorubicin was used as a model drug because a hydrophilic drug can release in water but is only slightly dissolved in 1-octanol during membrane formation. It was found doxorubicin from the EVAL membrane showed a two-step release behavior. The drug release in the first step was rapid. This is probably due to the membrane is macroscopically porous that drug distributing outside the particles diffuses out rapidly. On the contrary, the drug release in the second step was slow and prolonged. This is probably due to drug entrapped in the particle during membrane formation. However, the particle structure is microscopically dense enough to increase the diffusion resistance, thus delaying and lowering the drug release rate. Therefore, such a membrane could be useful for sustained release of hydrophilic drugs. In addition, a mathematical mass transfer model for a two-step release of doxorubicin from the particulate membrane was developed and applied to the analysis of the drug release data. It can be found that the spherical particles encapsulated more than 55% of the doxorubicin and had a very small mass transfer coefficient. These findings suggest that a drug delivery system using a particulate membrane is a promising method but the technique for loading drug in the particle requires further modification.