Image Analysis as a Tool for Fast Stability Screening of Solid Dispersions

Solid dispersion systems represent an attractive formulation route to achieve fast release of the active compound. Despite its promising potentials, recrystallization tendency of the amorphous dispersed drug is an issue of concern. This necessitates formulation and stability investigations with different polymers and drug polymer ratios. In early stability trials, preparation of thin solid dispersion films and investigation of these under polarized light microscopy for birefringence have shown to be fast and nondestructive way in screening formulation quality and stability of these systems [1]. Despite its usefulness, a quantitative method for measuring the degree of birefringence is lacking, limiting the full potential of polarized light microscopy for solid dispersion characterization. In the current study, we have developed a semi-automatic and user-friendly method for the estimation of number of birefringence spots and their relative coverage area on the image obtained from polarized light microscopy. The method comprises binarisation, morphological structuring, labeling connected component, area estimation of binary pixels and counting. Because air bubbles left on samples due to fast evaporation during film formation also gave raise to birefringence, a method is proposed to semi-automatically removing these bubble-related artifacts from images prior to estimation of birefringence from the crystallized drug. Image parameters estimated are subsequently used as responses in an experimental design and further used to investigate the importance of evaporation temperature, drug polymer ratio and polymer grades on solid dispersion stability. The suggested method provides insight and understanding of so far unanticipated role of evaporation rateon the stabilization of solid dispersion systems. Reference: [1] Eerdenbrugh B.v., Taylor L.S.; Small Scale Screening To Determine the Ability of Different Polymers To Inhibit Drug Crystallization upon Rapid Solvent Evaporation; Molecular Pharmaceutics 2010, 7(4): 1328-1337.