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