Modeling of the drug delivery from a hydrophilic transdermal therapeutic system across polymer membrane.

A mathematical simulation is presented which describes the in vitro drug delivery kinetics from hydrophilic adhesive water-soluble poly-N-vinylpyrrolidone (PVP)-polyethylene glycol (PEG) matrices of transdermal therapeutic systems (TTS) across skin-imitating hydrophobic Carbosil membranes. Propranolol is employed as the test drug. The contributions of the following physicochemical determinants to drug delivery rate control have been estimated: the drug diffusion coefficients both in the matrix and the membrane; the membrane-matrix drug partition coefficient: the drug concentration in the matrix and the membrane thickness. Drug transfer from the hydrophilic matrix across the membrane is shown to be controlled by the drug partitioning from the matrix into the membrane. The best correlation between simulation data and experimental results is obtained when the effect of membrane hydration is taken into consideration during in vitro drug release.