Polymerization of naturally occurring isohexenylnaphthazarins (IHN), such as alkannin, shikonin (A/S) and their derivatives, which are potent pharmaceutical substances, significantly affects their use in pharmaceuticals, cosmetics and as food colorants, because it leads to reduction of the lustre of their red coloration, a decrease in their solubility and reduces the active monomeric IHN derivatives. In the present study, the influence of several crucial variables (processing and storage) was experimentally investigated on IHN polymerization by size exclusion chromatography (SEC). Temperature and solvent polarity increased significantly the concentration of hydroxynaphthoquinone (HNQ) polymers, while air and light exposure conditions did not significantly affect IHN polymerization. Low temperatures are proposed for all processes of industrial production of pharmaceutical preparations containing IHN and HNQ. An optimization of the industrial conditions used for the preparation of pharmaceutical and cosmetic preparations containing IHN, maximizing the active monomeric IHN fraction, was performed.