Fractal aggregation of dihydroquercetin after lyophilization

Purpose: Fractal geometry is a relatively young mathematical concept, which has been gradually implemented in various fields of human activity. The focus of this article lies on using this powerful tool for monitoring and forecasting the water solubility of dihydroquercetin (DHQ) and its new forms, which were obtained by lyophilization with different coformers. DHQ, also known as taxifolin, is the major flavonoid of larch wood. This compound prevents the accumulation of free radicals and is characterized by a wide range of pharmacological effects. DHQ is produced industrially and is registered in Russia as an active pharmaceutical ingredient (API). Methods: DHQ co-crystals with different coformers were generated by lyophilization. The fractal dimensions of the lyophilizates were measured by photomicrography processing with special software. The water solubility was determined according to the European Pharmacopoeia 8.0. Results: It was established that the solid phases of the DHQ lyophilizates generate specific structures that agglomerate in different fractals. A correlation was shown between the DHQ fractal dimension and its water solubility. The correlation coefficient was 0.94. The relative standard deviation was no more than 1.17%. Conclusions: This study demonstrated the ability to predict the water solubility of DHQ forms by measurement of the fractal dimensions. The fractal model can find wide application in the pharmaceutical industry as a tool for automating quality assays without substance loss.