Sandra Jankovic1,2, Georgia Tsakiridou3,4, Felix Ditzinger1,2, Niklas J Koehl5, Daniel J Price6,7, Alexandra-Roxana Ilie5,8, Lida Kalantzi3, Kristof Kimpe9, René Holm8, Anita Nair6, Brendan Griffin5, Christoph Saal6, Martin Kuentz2. 1. Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland. 2. Institute of Pharma Technology, University of Applied Sciences and Arts Northwestern Switzerland, Muttenz, Switzerland. 3. Pharmathen SA, Product Design & Evaluation, Athens, Greece. 4. Faculty of Pharmacy, National and Kapodistrian University of Athens, Athens, Greece. 5. School of Pharmacy, University College Cork, Cork, Ireland. 6. Merck Group, Molecule Characterisation, Darmstadt, Germany. 7. Goethe University, Frankfurt, Germany. 8. Drug Product Development, Janssen Research and Development, Johnson & Johnson, Beerse, Belgium. 9. Pharmaceutical Sciences, Janssen Research and Development, Johnson & Johnson, Beerse, Belgium.
Abstract
OBJECTIVES: 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. KEY FINDINGS: 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. SUMMARY: 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.
OBJECTIVES: 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. KEY FINDINGS: 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. SUMMARY: 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.