Application of the solubility parameter concept to assist with oral delivery of poorly water-soluble drugs – a PEARRL review

Sandra Jankovic, Georgia Tsakiridou, Felix Ditzinger, Niklas J Koehl, Daniel J Price, Alexandra-Roxana Ilie, Lida Kalantzi, Kristof Kimpe, René Holm, Anita Nair, Brendan Griffin, Christoph Saal, Martin Kuentz

Solubility parameters have been used for decades in various scientific fields including pharmaceutics. It is, however, still a field of active research both on a conceptual and experimental level. This work addresses the need to review solubility parameter applications in pharmaceutics of poorly water-soluble drugs. An overview of the different experimental and calculation methods to determine solubility parameters is provided, which covers from classical to modern approaches. In the pharmaceutical field, solubility parameters are primarily used to guide organic solvent selection, cocrystals and salt screening, lipid-based delivery, solid dispersions and nano- or microparticulate drug delivery systems. Solubility parameters have been applied for a quantitative assessment of mixtures, or they are simply used to rank excipients for a given drug. In particular, partial solubility parameters hold great promise for aiding the development of poorly soluble drug delivery systems. This is particularly true in early-stage development, where compound availability and resources are limited. The experimental determination of solubility parameters has its merits despite being rather labour-intensive because further data can be used to continuously improve in silico predictions. Such improvements will ensure that solubility parameters will also in future guide scientists in finding suitable drug formulations.