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Solubility_18polymers_ChemRxiv.pdf (30.88 MB)

Like Dissolves Like? A Comprehensive Evaluation of Partial Solubility Parameters to Predict Polymer-Drug Compatibility in Ultra-High Drug Loaded Polymer Micelles

submitted on 29.04.2019 and posted on 30.04.2019 by Michael M Lübtow, Malik Salman Haider, Marius Kirsch, Stefanie Klisch, Robert Luxenhofer

Despite decades of research, our understanding of the molecular interactions between drugs and polymers in drug loaded polymer micelles does not extend much beyond concepts such as “like-dissolves-like“ or hydrophilic/hydrophobic. However, polymer-drug compatibility strongly affects formulation properties and therefore the translation of a formulation into the clinics. Specific interactions such as hydrogen-bonding, π-π stacking or coordination interactions can be utilized to increase drug-loading. This is commonly based on trial-and-error and eventually leads to an optimized drug carrier. Unfortunately, due to the unique characteristics of each drug, the deduction of advanced general concepts remains challenging. Furthermore, the introduction of complex moieties or specifically modified polymers hampers systematic investigations regarding polymer drug-compatibility as well as clinical translation. In this study, we reduced the complexity in order to isolate crucial factors determining drug-loading. Therefore, the compatibility of 18 different amphiphilic polymers for 5 different hydrophobic drugs was determined empirically. Subsequently, the obtained specificities were compared to theoretical compatibilities derived from either the Flory-Huggins interaction parameter or Hansen solubility parameters. In general, Flory-Huggins interaction parameters were less suited to correctly estimate the experimental drug solubilization compared to the Hansen solubility parameters. The latter were able to correctly predict some trend regarding good and poor solubilizers, yet the overall predicitive strength of Hansen Solubility parameters is clearly unsatisfactory.


Deutsche Forschungsgemeinschaft

Evonik Foundation


Email Address of Submitting Author


University of Würzburg



ORCID For Submitting Author


Declaration of Conflict of Interest

MML and RL are listed as inventors on subject matter pertinent to this publication. RL is also co-founder of DelAqua Pharmaceuticals Inc. which aims at commercialization of materials described herein.

Version Notes

first version submitted for peer review