Methods for the preparation of amorphous solid dispersions - A comparative study

Solid dispersion is considered one of the most successful strategies for improving the dissolution and absorption of poorly water-soluble APIs. The primary focus of this study was to investigate the effects of methods of solid dispersion preparation on the pharmaceutically important physicochemical properties of a product based on Soluplus® as the polymer carrier and febuxostat as the model BCS II API. The methods of preparation evaluated were based on melt and solvent mechanisms. The samples prepared were evaluated by modulated differential scanning calorimetry, solid state NMR, Raman spectroscopy, XRPD, scanning electron microscopy, and BET analysis. Differences among the solid dispersions obtained by the specific methods and their mechanisms were clearly observed in in-vitro testing. The dissolution behaviour was shown to be influenced not only by particle characteristics such as the size and specific surface area, but also by the interactions between the API and the polymer matrix on the molecular level (e.g. non-covalent interactions). The set of measurements showed that similar methods of preparation do not lead to solid dispersion systems of similar characteristics. Surprisingly, similar dissolution profiles were found in samples prepared by very different methods although their physical-chemical characteristics differed significantly, and vice versa.

Physical and chemical characteristics of the solid dispersion samples (left) and their influance on in-vitro performance (right).185