Anomalous role change of tertiary amino and ester groups as hydrogen acceptors in eudragit E based solid dispersion depending on the concentration of naproxen.

Eudragit E (EGE) is a basic polymer incorporating tertiary amino and ester groups. The role of the functional groups of EGE in the formation of solid dispersion (SD) with Naproxen (NAP) was investigated. The glass transition temperature (Tg) of EGE decreased with the plasticizing effect of NAP up to 20% weight ratio. Addition of NAP at over 30% induced a rise in Tg, with the maximum value being reached at 60% NAP. Further addition of NAP led to a rapid drop of the Tg. A dramatic difference of physical stability between the SDs including 60 and 70% NAP was confirmed. The SD including 70% NAP rapidly crystallized at 40 °C with 75% relative humidity, while the amorphous state could be maintained over 6 months in the SD with 60% NAP. The infrared and (13)C solid state-NMR spectra of the SDs suggested a formation of ionic interaction between the carboxylic acid of NAP and the amino group of EGE. The SD with 20% NAP raised the (13)C spin-lattice relaxation (T1) of the amino group, but it decreased with over 30% NAP. The change in the (13)C-T1 disappeared with 70% NAP. The (13)C-T1 of the ester group rose depending on the amount of NAP. From these findings, we concluded that the role as hydrogen acceptor shifted from the amine to the ester group with an increase in amount of NAP. Furthermore, the amino group of EGE did not contribute to the interaction at over 70% NAP. These phenomena could be strongly correlated with Tg and stability.