Miscibility studies of indomethacin and Eudragit® E PO by thermal, rheological, and spectroscopic analysis

The objective of this study is to understand the underlying mechanisms responsible for the superior stability of indomethacin (INM)-Eudragit® E PO (E PO) system by exploring the miscibility and intermolecular interactions through the combination of thermal, rheological, and spectroscopic analysis. The zero shear-rate viscosity drops monotonically with the increase of INM concentration at 145°C, suggesting that E PO and INM form a solution and the small molecular drug acts as a plasticizer. Flow activation energy was calculated from the viscosity data at different temperature. The glass transition temperature (T_g) of the mixture at different composition was determined using differential scanning calorimetry. The T_g and flow activation energy peak at the INM concentration around 60%-70%. Fourier transform infrared analysis provided direct evidence for the intermolecular ionic interactions, which may disrupt the dimer formation of amorphous INM. The study explained the superior stability of INM-E PO mixtures, and demonstrated that a combination of thermal, rheological, and spectroscopic technologies can help us to obtain a full picture of the drug-polymer interactions and to determine the formulation and processing conditions.