Control of drug concentration-time profiles in vivo by zero-order transdermal delivery systems

Control of 9-β-arabinofuranosyladenine (ara-A) and ara-A-2',3'-diacetate (ara-ADA) concentrations in blood from zero-order transdermal delivery systems was achieved using newly designed transdermal patches with rate-limiting membranes. Membrane permeability coefficients were altered by changing copolymer compositions of 2-hydroxyethyl methacrylate (HEMA) with styrene (St) or N-vinylpyrrolidone (VP). The copolymers compositions were chosen according to the hydration properties of the membrane.In vitro permeability coefficients of 5 × 10⁻⁶, 1 × 10⁻⁶, 5 × 10⁻⁷and 1 × 10⁻⁷ cm/s were obtained for ara-A and ara-ADA with the membranes used in the transdermal patches. In vivo blood levels of the total drug (i.e., drug plus metabolites) were monitored following application of the patch on Azone pretreated abdominal sites of hairless mice. The drug concentration-time profiles agreed with the values predicted from the theoretical model developed from the in vitro studies.