This work aimed to evaluate the flexibility of a novel pyrolytic carbon coated drug-eluting stent platform, which presents the peculiarity of deep sculptures realized on the stent's outer surface (reservoirs). Tacrolimus (TCR) or TCR/excipient mixtures were loaded into the reservoirs, and their permanence into stent's reservoirs was verified by an in vitro short-time release test in human blood. Moreover, the impact of the excipients on the TCR physical state and surface morphology of the reservoirs and the release kinetics were studied. The reservoirs resulted homogeneously filled. Upon exposure to blood, no loss of materials from reservoirs was observed, and the drug release after 15 min was negligible in all cases. The loading procedure caused the drug amorphization and, AFM revealed that the surfaces were smooth and homogeneous with the exception of the TCR/poloxamer 188 mixture where spatial oriented crystals were evident. Poly(N-vinyl pyrrolidone) improved the in vitro TCR release rate constants (K). Poly(methylmethacrylate) (PMM) significantly reduced the K value both in vitro and in vivo. Indeed, the in vivo drug concentrations in rabbit artery wall significantly decreased, decreasing the TCR/PMM ratio. The characteristics of the stent strut resulted suitable to load material with different physicochemical characteristics.