Qualitative and quantitative methods to determine miscibility in amorphous drug-polymer systems

Abstract

Amorphous drug-polymer systems or amorphous solid dispersions are commonly used in pharmaceutical industry to enhance the solubility of compounds with poor aqueous solubility. The degree of miscibility between drug and polymer is important both for solubility enhancement as well as for the formation of a physically stable amorphous system. Calculation of solubility parameters, Computational data mining, Tg measurements by DSC and Raman mapping are established traditional methods used to qualitatively detect the drug-polymer miscibility. Calculation of Flory-Huggins interaction parameter, computational analysis of X-Ray Diffraction (XRD) data, solid state Nuclear Magnetic Resonance (NMR) spectroscopy and Atomic Forced Microscopy (AFM) have been recently developed to quantitatively determine the miscibility in amorphous drug-polymer systems. This brief review introduces and compiles these qualitative and quantitative methods employed in the evaluation of drug-polymer miscibility. Combination of these techniques can provide deeper insights into the true miscibility of the drug-polymer systems.

Keywords: Amorphous; Atomic force microscopy; Computational; Glass transition; Interaction parameters; Melting point depression; Miscibility; NMR; Raman; Solid dispersion; Solubility parameters; X-ray diffraction.