Thermoanalytical and Fourier transform infrared spectral curve-fitting techniques used to investigate the amorphous indomethacin formation and its physical stability in Indomethacin-Soluplus® solid dispersions

Abstract

The amorphous form of a drug has higher water solubility and faster dissolution rate than its crystalline form. However, the amorphous form is less thermodynamically stable and may recrystallize during manufacturing and storage. Maintaining the amorphous state of drug in a solid dosage form is extremely important to ensure product quality. The purpose of this study was to quantitatively determine the amount of amorphous indomethacin (INDO) formed in the Soluplus® solid dispersions using thermoanalytical and Fourier transform infrared (FTIR) spectral curve-fitting techniques. The INDO/Soluplus® solid dispersions with various weight ratios of both components were prepared by air-drying and heat-drying processes. A predominate IR peak at 1683cm−1 for amorphous INDO was selected as a marker for monitoring the solid state of INDO in the INDO/Soluplus® solid dispersions. The physical stability of amorphous INDO in the INDO/Soluplus® solid dispersions prepared by both drying processes was also studied under accelerated conditions. A typical endothermic peak at 161°C for γ-form of INDO (γ-INDO) disappeared from all the differential scanning calorimetry (DSC) curves of INDO/Soluplus® solid dispersions, suggesting the amorphization of INDO caused by Soluplus® after drying. In addition, two unique IR peaks at 1682 (1681) and 1593 (1591)cm−1 corresponded to the amorphous form of INDO were observed in the FTIR spectra of all the INDO/Soluplus® solid dispersions. The quantitative amounts of amorphous INDO formed in all the INDO/Soluplus® solid dispersions were increased with the increase of γ-INDO loaded into the INDO/Soluplus® solid dispersions by applying curve-fitting technique. However, the intermolecular hydrogen bonding interaction between Soluplus® and INDO were only observed in the samples prepared by heat-drying process, due to a marked spectral shift from 1636 to 1628cm−1 in the INDO/Soluplus® solid dispersions. The INDO/Soluplus® solid dispersions prepared by both drying processes could keep the amorphous state of INDO in the INDO/Soluplus® solid dispersions at the accelerated storage condition.