Related Experiment Video
Updated: May 5, 2026

Solubility of Hydrophobic Compounds in Aqueous Solution Using Combinations of Self-assembling Peptide and Amino Acid
Published on: September 20, 2017
Solubility Enhancement of Active Pharmaceutical Ingredients through Liquid Hydrotrope Addition: A Thermodynamic
Sahar Nasrallah1, Mirjana Minceva1
1Biothermodynamics, TUM School of Life Sciences, Technical University of Munich, Maximus-von Imhof-Forum 2, Freising 85354, Germany.
Abstract:
The poor water solubility of active pharmaceutical ingredients (APIs) poses a significant challenge in pharmaceutical development, affecting their bioavailability and therapeutic efficacy. Consequently, there is an urgent demand for strategies to improve API solubility, with hydrotropy emerging as one of the most effective approaches. Hydrotropes, which can act as excipients in pharmaceutical formulations, enhance solubility by solubilizing hydrophobic compounds in aqueous solutions through mechanisms other than micellar solubilization. However, identifying the right hydrotropic agent requires a screening from a large pool of candidates. This work aims to analyze hydrotropy from a thermodynamic perspective by investigating the influence of the molecular interactions among the API, hydrotrope, and water on the API solubility in water at different temperatures. For this systematic study, hypothetical ternary systems were used and only liquid hydrotropes were considered. Utilizing the Two-Suffix Margules equation to model the liquid phase nonideality, the study revealed that strong API-hydrotrope interactions notably enhance the API solubility in water. Additionally, the interaction between the hydrotrope and water significantly influences API solubility; weaker hydrotrope-water interactions allow for increased API solubility in water. However, when hydrotrope-water interactions are stronger than API-hydrotrope interactions, this effect is diminished. The theoretical findings were validated using solubility experimental data of syringic acid with alkanediols in water from the literature. The results of this work will aid in selecting suitable liquid hydrotropes for enhancing the API solubility in aqueous solutions.
Related Concept Videos
Enthalpy of Solution
Factors Influencing Drug Absorption: Pharmaceutical Parameters
Bioavailability Enhancement: Determination and Conceptual Approaches in Overcoming Bioavailability Problems
Bioavailability Enhancement: Drug Solubility Enhancement
Bioavailability Enhancement: Drug Permeability Enhancement
Bioavailability Enhancement: Drug Stability Enhancement and GI Retention

