This research extends the understanding of lidocaine conformer distributions under various isobaric conditions (10, 20, and 30 MPa) and temperatures (35, 50, and 70 °C). Employing quantum chemical calculations and NOESY spectroscopy, the study explores the influence of lidocaine conformers on micronized particle sizes. Results reveal that Trans-conformers, stabilized by intramolecular hydrogen bonds, dominate under specific conditions, impacting the formation of lidocaine dimers. The NOESY analysis demonstrates consistent conformer proportions, highlighting the stability of ethyl fragment positions. These findings contribute significantly to comprehending lidocaine's behavior during the rapid expansion from supercritical to aqueous solution (RESAS) process, offering crucial insights for pharmaceutical formulation design.
