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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.

Harmonizing unit operations in the downstream process of monoclonal antibodies (mAbs) has a high potential to overcome throughput limitations and reduce manufacturing costs. This study proposes a streamlined clarification and capture (S-CC) process concept for the continuous processing of cell broth harvested from a connected bioreactor. The process was realized with a fluidized bed centrifuge connected to depth and sterile filters, a surge tank, and a multi-column chromatography (MCC) unit. The MCC unit was operated in the rapid cycling simulated moving bed (RC-BioSMB) mode with five convective diffusive membrane adsorbers (MAs). A control strategy and the surge tank were used to adjust the loading flow rate of the MCC unit. The mAb was recovered with a total process yield of 90%, with high removal of the process-related impurities HCP (2.1 LRV) and DNA (2.9 LRV). Moreover, the S-CC process productivity of 4.2 g h - 1 was up to 5.3 times higher than for comparable, hypothetical batch MA processes. In addition, the buffer consumption of the capture step could be reduced from 2.0 L g - 1 in batch mode to 1.2 L g - 1 in the RC-BioSMB mode. These results demonstrate the high potential of streamlined interconnected unit operations to improve the overall mAb downstream process performance., (© 2024 The Author(s). Biotechnology and Bioengineering published by Wiley Periodicals LLC.)

Oleaginous microorganisms are promising for the biotechnological production of valuable hydrophobic bioactive components. For an environmentally friendly extraction, we evaluated a two-step process for β-carotene and lipid isolation from wet Rhodosporidium toruloides biomass using biphasic green and biobased solvent systems: 2-methyl tetrahydrofuran (2-MeTHF) or cyclopentyl-methyl-ether (CPME) with ethanol or 1-butanol and water. Initially, components were extracted with a single-phase solvent mixture, followed by separating hydrophobic target components from polar impurities via phase separation. We employed the Conductor-like Screening Model for Real Solvents (COSMO-RS) to predict the solubility of β-carotene and select compositions with higher solubility. Our study highlights the potential of these solvent systems for extracting hydrophobic components and the importance of understanding the system's liquid-liquid equilibria for effective process design. We present a framework for evaluating new solvent systems for extracting hydrophobic bioactive compounds by demonstrating the impact of solvent composition selection on extraction yields and solvent consumption., Competing Interests: The authors declare no competing financial interest., (© 2025 The Authors. Published by American Chemical Society.)