The Effect of Adding PVP to the Binary Solid Dispersion (Indomethacin: Kaolin) on the Formation of Physically Stable Amorphous Drug

In this work, we investigate the effect of adding polyvinylpyrrolidone (PVP K30) to the binary solid dispersion (indomethacin/kaolin) on the formation of physically stable amorphous drug. This aims to profit more effectively from the therapeutic effect of kaolin in the solid dosage forms of indomethacin. Binary mixtures (indomethacin/kaolin) were ball milled at room temperature (≈ 25 °C) in presence of PVP K30 at different weight ratios (w/w). The characterization of the obtained materials was carried out using X-ray diffraction (XRD), infrared spectroscopy (FTIR), scanning electronic microscopy (SEM), high-performance liquid chromatography (HPLC), differential scanning calorimetry (DSC), and 13C MAS NMR spectroscopy. Results have shown that indomethacin (IND) interacted with kaolin and PVP K30 in solid state via hydrogen bonds without any polymorphic transformations or chemical degradation. The PVP seems to play a role of linker between drug and kaolin leading to physical stability enhancement of amorphous IND even under high stress conditions (RH = 75% and T = 40 °C for 3 months). Such ternary system (IND/kaolin/PVP) has shown a considerable improvement of drug solubility at T = 37 ± 0.5 °C and pH = 7.0 compared to the binary solid dispersion (IND/kaolin). The addition of PVP to the solid dispersion (IND/kaolin) was advantageous not only in terms of physical stabilization of the amorphous IND but also made it possible to overcome the solubility challenges associated with the presence of kaolin.