Summary of the Master Thesis

Indomethacin (IND) is classified in class II of the Biopharmaceutics Classification System (BCS), meaning it exhibits good permeability, but poor solubility. By using the amorphous form of the drug higher apparent solubility can be obtained, but the challenge of crystallization from supersaturated solutions remains. The main aim of this study was to investigate the level and maintenance of supersaturated solutions, with respect to the thermodynamic solubility of crystalline IND, of the amorphous form of the drug. Some experimental conditions of the method were fine-tuned.

Crystalline and amorphous IND were characterised using different analytical techniques, including infrared (IR) spectroscopy, Raman spectroscopy and differential scanning calorimetry (DSC). Crystallization behaviour was studied using polarized light microscopy (PLM) and IR spectroscopy.

During the solubility studies two different polymers (HPMC and Soluplus®) were used in a drug:polymer 1:1 ratio (w/w). The maximum drug concentrations (Cmax) generated with the suspensions containing the respective predissolved polymer were considerably higher for Soluplus® compared to HPMC. Soluplus® also showed a higher potential in maintaining supersaturated solutions compared to HPMC.

The permeation of IND in the presence of polymer through an artificial membrane as well as the potential impact of permeation on the maintenance of supersaturation was investigated. The concentration of dissolved IND in the donor compartment decreases for each suspension. However, no IND could be measured in the acceptor compartment. The impact of permeation on the maintenance of supersaturation was dependent on the polymer used: for HPMC supersaturation was maintained longer during the permeation studies than during the solubility studies while for Soluplus® the opposite was observed.