Structural phenomena in hydrogel-drug systems

Crystallization and structural transition in a cross-linked poly(ethylene oxide) 4000 (PEO) polymer were investigated as functions of water content and concentration of model drugs (acetaminophen and caffeine) using small angle X-ray scattering (SAXS) and wide angle X-ray scattering (WAXS) techniques. In the hydrated state (300 wt% of water), gel retains an ordering with characteristic spacing of 80 Å. With a water concentration of about 20%, this structure undergoes transition into lamellae with long spacing of 200 Å and then into semi-crystalline polymer matrix when water content is below 5%. This transition is associated with different type of phase separations, first, between crystalline and amorphous PEO domains in the dry polymer and, second, between water and hydrophobic cross-linked regions in the swollen gel. Because of a specific hydrogen bonding, acetaminophen forms a molecular complex with the PEO, a drug concentration as small as 1% resulting in a significant increase of the long spacing and decrease of crystallinity of the polymer. Caffeine precipitates in the form of crystalline particles and also reduces the crystallinity of the polymer matrix.