Aqueous solubility is a fundamentally important property that affects not only the potential for API absorption after oral administration but also the ability to administer the API parenterally. Parenteral formulation design is a key component in almost all discovery and development programs (regardless of the intended route of clinical administration) since data obtained after intravenous administration is necessary to generate fundamental pharmacokinetic information to support compound optimisation and progression.
Low aqueous solubility significantly complicates the development of intravenous formulations since, in almost all cases, simple solution formulations are required. This precludes the use of formulation approaches that are commonly used to enhance bioavailability via the oral route (nanosuspensions, amorphous solid dispersions) and limits the formulation toolbox to solubilisation approaches like pH adjustment, the use of cosolvent/surfactant combinations, lipid-based systems or cyclodextrin formulations. However, these technologies fail to solubilise many poorly soluble APIs in sufficiently high concentrations in the formulation, utilise poorly tolerated excipients (especially cosolvents are notorious in this regard) and may rapidly lose solvent capacity when diluted in blood, which may tigger side effects and affect API distribution.
The tunability offered by our deep eutectic solvent technology creates unique advantages to tackle these challenges associated with intravenous administration of poorly soluble APIs:
- API loadings that are unparellelled by any of the traditional solubilisation technologies
- Applicable across all API chemistries
- Solvent capacity derived from multiple excipients rather than one single excipient, which improves the tolerability profile of the formulation
- Ease of manufacture, enabling short turnaround times compatible with the timelines in discovery, preclinical and early clinical settings
- Retention of solvent capacity at low dilution levels, which reduces precipitation risk after administration and enables precipitation-free dilution with saline prior to administration