In the present study, a pyrrolidone adhesive and an amide adhesive were synthesized, and their molecular mechanisms of controlled drug release were described. Using zolmitriptan as model drug, in vitro drug release and skin permeation experiments were performed. Adhesive properties were evaluated using modulated differential scanning calorimetry and rheology study. Free volume of polymer was directly obtained by positron annihilation lifetime spectroscopy. Intermolecular interactions between drugs and adhesives were determined by FTIR spectroscopic analysis and molecular simulation. Release percent (24 h) of zolmitriptan from pyrrolidone adhesive was about 55.8 ± 3.1% (w/w), while from amide adhesive, the release percent (24 h) was about 40.1 ± 1.6% (w/w). The free volume sizes of pyrrolidone adhesive and amide adhesive were about 2309.6 Å3 and 2854.5 Å3, respectively, which were much larger than molecular volume of zolmitriptan (about 285.7 Å3). Thus, the polymer networks might not hinder drug diffusion from the view of free volume. Comparing chemical structures of pyrrolidone group and primary amide group, the main difference was that primary amide group of amide adhesive possessed 2 hydrogen donors. It was proved that hydrogen bonding between zolmitriptan and hydrogen donor of primary amide group played a critical role in controlling drug release.
Keywords: controlled release; drug delivery system; drug-excipient interaction; polymer; transdermal.
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