VEHICLE-DEPENDENT IN-SITU MODIFICATION OF MEMBRANE-CONTROLLED DRUG-RELEASE

The possibility of utilizing the interaction between the drug vehicle and the polymeric control membrane of reservoir-type drug delivery sys tems to modulate the release rate of these systems was investigated. L ipid vehicles common in dermal formulations, with varying composition and viscosity and the Celgard(R) polypropylene membrane were used to s tudy the release of a model drug (salicylic acid). The release kinetic s were investigated taking into account two consecutive transport proc esses, diffusion within the donor reservoir and permeation through the membrane. Membrane permeation was found to be the rate determining st ep for mass transport and convection appeared to play a significant ro le in the donor compartment, even though this compartment was not mech anically stirred. The lipid vehicles were imbibed by the membrane, qua ntitatively replacing the air from its pores. Drug permeation through the membrane was dominated by the vehicle-filled pore pathway, the pat hway of the amorphous polymer domain of the membrane generally contrib uting a small fraction to the total permeation. Permeability coefficie nts for different vehicles varied within one order of magnitude. This effect was chiefly accounted for by the differences in viscosity of th e vehicles occupying the pores of the membrane. Thus, based on the in situ imbibition of the lipid vehicles by the membrane, a controlled va riation of the drug release rate could be achieved. (C) 1998 Elsevier Science B.V.