Synthesis of poly(sebacic anhydride)-indomethacin controlled release composites via supercritical carbon dioxide assisted impregnation

Abstract

Poly(sebacic anhydride), PSA and indomethacin drug composite (DC) formulations were prepared using supercritical CO 2 (sc-CO 2) aided mixing. The effect of the experimental temperature and sebacic acid purity on the physical properties of PSA–indomethacin DCs was investigated using a range of analytical techniques. The nature of the PSA–indomethacin interaction in composites after processing in sc-CO 2 under various conditions was investigated using differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy, and powder X-ray diffraction (XRD) methods, respectively. The results indicate that processing at 130 °C of a 4:1 (w/w) ratio PSA–indomethacin mixture, renders the indomethacin amorphous and dispersed within the polymer matrix. The primary interaction between PSA and indomethacin appears to be hydrogen bonding between the carboxylic acid OH of indomethacin and the carbonyl group of PSA. In vitro dissolution studies revealed that the processed composites exhibit a substantially enhanced dissolution rate compared to the physical mixtures. Also, through the control of experimental conditions, the initial burst effect of the drug release was largely alleviated. Instead, the erosion of PSA (zero order degradation) became the dominant factor in controlling the drug release rate.