A microfluidic platform for pharmaceutical salt screening.

Area of Science:

• Pharmaceutical Sciences
• Chemical Engineering
• Materials Science

Background:

• Pharmaceutical salt screening is crucial for drug development.
• High-throughput screening methods often require large volumes of parent compounds (PCs).
• Developing new salt forms can improve drug solubility, stability, and bioavailability.

Purpose of the Study:

• To develop and validate a novel microfluidic platform for efficient pharmaceutical salt screening.
• To significantly reduce the volume of pharmaceutical parent compound (PC) solution needed for screening.
• To enable on-chip analysis and identification of pharmaceutical salts.

Main Methods:

• A 48-well microfluidic platform was designed for combinatorial screening of pharmaceutical parent compounds (PCs) and salt formers (SFs).
• On-chip mixing in 87.5-nanolitre wells was achieved using diffusive and/or convective methods.
• Solvent loss was minimized using thin polydimethylsiloxane (PDMS) layers and impermeable top/bottom layers, with pneumatic valves for well isolation.
• On-chip analysis utilized brightfield and polarized light microscopy, coupled with Raman spectroscopy on a gold-coated glass substrate for enhanced signal-to-noise ratio.

Main Results:

• The microfluidic platform demonstrated a drastic reduction in PC solution volume requirements.
• Validation using naproxen (acid) and ephedrine (base) successfully identified four naproxen salts and five ephedrine salts.
• Optimized PDMS layer thickness and substrate coating improved the signal-to-noise ratio for Raman spectroscopy.

Conclusions:

• The developed microfluidic platform offers a highly efficient and low-volume method for pharmaceutical salt screening.
• The system facilitates rapid identification and characterization of novel pharmaceutical salts on-chip.
• This technology has the potential to accelerate drug development by optimizing salt selection processes.