title: Miscibility studies of indomethacin and Eudragit® E PO by thermal, rheological, and spectroscopic analysis.
abstract: 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.
authors.affiliation: Otto York Department of Chemical, Biological and Pharmaceutical Engineering, New Jersey Institute of Technology, Newark, New Jersey 07102, USA.
authors.forename: Huiju
authors.initials: H
authors.lastname: Liu
authors.forename: Xueyan
authors.initials: X
authors.lastname: Zhang
authors.forename: Herman
authors.initials: H
authors.lastname: Suwardie
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.forename: Costas G
authors.initials: CG
authors.lastname: Gogos
mesh_terms: D002152:Calorimetry, Differential Scanning; D007213:Indomethacin / Q000737:chemistry*; D011109:Polymethacrylic Acids / Q000737:chemistry*; D012212:Rheology; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013696:Temperature
chemical_list: D011109:Polymethacrylic Acids; C038300:methylmethacrylate-methacrylic acid copolymer; D007213:Indomethacin