Hot melt mixing and foaming of soluplus® and indomethacin

The hot melt mixing (HMM) process was used to dissolve 30 wt% of a model drug, indomethacin (INM), in Soluplus® a water soluble polymer excipient. Comprehensive characterization of the HMM-prepared samples, using differential scanning calorimetry, X-ray diffraction, Fourier Transform Infrared spectroscopy, and optical microscopy, strongly suggests that INM was in amorphous state, forming a solid solution with the polymer. Furthermore, to understand the impact of foaming on INM's release profile, the HMM product was foamed in a batch process using supercritical carbon dioxide (CO₂). Dissolution tests of HMM and reference samples were conducted in aqueous solutions with pH 7.4 and 1.2. In all cases INM's release showed strong pH-dependency; faster release and a greater amount of INM was released at pH 7.4 than at pH 1.2. For pure INM and the physical mixture, the drug's ionizable character results in the observed pH-dependency. While for the HMM samples it is also a consequence of theformation of hydrogen bonds between Soluplus® and INM which hinder polymer dissolution at pH 1.2. It was observed that the release rate of INM from different sample types at pH 7.4 decreased in the following sequence: foamed HMM > unfoamed HMM > crystalline INM > physical mixture. POLYM. ENG. SCI., 2012. © 2012 Society of Plastics Engineers