Poly(2-oxazoline)- and Poly(2-oxazine)-Based Formulation Library Reveals Limits of Solubility Parameter-Based Drug-Polymer Compatibility Prediction.

Authors

Malik Salman Haider, Robert Luxenhofer

Published in

Biomacromolecules. Volume 27. Issue 11. Pages 7767-7787. Nov 09, 2026.

Abstract

Four structurally related poly(2-oxazoline) (POx)- and poly(2-oxazine) (POzi)-based ABA triblock copolymers were evaluated across 21 poorly water-soluble drugs to assess whether Hansen solubility parameters (HSPs) predict polymer-specific formulation performance. HSPs were calculated using Hoftyzer-Van Krevelen (HnV) and Yamamoto molecular break (YMB) methods, with semi-empirical polymer HSPs derived from solvent-solubility profiles. The polymers showed drug-specific performance, with maximum loading capacities exceeding 40 wt % for four drugs and 30 wt % for another four drugs. However, Ra showed limited discriminatory power. Among 20 drugs with YMB-derived Ra values, the lowest-Ra polymer was experimentally best for only 4 (20%), while Ra-based and experimental within-drug pairwise rankings agreed in 59 of 119 comparisons (49.6%). Significant cross-drug correlations for two polymers were positive, opposite to the expected trend. Despite this limited predictive performance, the resulting formulation library provides a broad experimental platform for identifying polymer-drug combinations for subsequent application-specific preclinical development.

PMID:
43002029
Bibliographic data and abstract were imported from PubMed on 09 Nov 2026.

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