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 systems to modulate the release rate of these systems was investigated. Lipid vehicles common in dermal formulations, with varying composition and viscosity and the Celgard(R) polypropylene membrane were used to study the release of a model drug (salicylic acid). The release kinetics were investigated taking into account two consecutive transport processes, diffusion within the donor reservoir and permeation through the membrane. Membrane permeation was found to be the rate determining step for mass transport and convection appeared to play a significant role in the donor compartment, even though this compartment was not mechanically stirred. The lipid vehicles were imbibed by the membrane, quantitatively replacing the air from its pores. Drug permeation through the membrane was dominated by the vehicle-filled pore pathway, the pathway of the amorphous polymer domain of the membrane generally contributing a small fraction to the total permeation. Permeability coefficients for different vehicles varied within one order of magnitude. This effect was chiefly accounted for by the differences in viscosity of the vehicles occupying the pores of the membrane. Thus, based on the in situ imbibition of the lipid vehicles by the membrane, a controlled variation of the drug release rate could be achieved. (C) 1998 Elsevier Science B.V.