Effects of polymeric additives on the crystallization and release behavior of amorphous ibuprofen

摘要

Some polymeric additives were studied to understand their effects on the amorphous phase of ibuprofen (IBU), used as a poorly water soluble pharmaceutical model compound. The amorphous IBU in bulk, as well as in nanopores (diameter 24 nm) of anodic aluminum oxide, was examined with the addition of poly(acrylic acid), poly(N-vinyl pyrrolidone), or poly(4-vinylphenol). Results of bulk crystallization showed that they were effective in limiting the crystal growth, while the nucleation of the crystalline phase in contact with water was nearly instantaneous in all cases. Poly(N-vinyl pyrrolidone), the most effective additive, was in specific interaction with IBU, as revealed by IR spectroscopy. The addition of the polymers was combined with the nanoscopic confinement to further stabilize the amorphous phase. Still, the IBU with addition of polymeric additives showed sustained release behavior. The current study suggested that the inhibition of the crystal nucleation was probably the most important factor to stabilize the amorphous phase and fully harness its high solubility.