This study describes the preparation, characterization, and influence of the enantiopure vs. racemic coformer on the physico-chemical properties of a pharmaceutical cocrystal. For that purpose, two new 1:1 cocrystals, namely lidocaine:dl-menthol and lidocaine:d-menthol, were prepared. The menthol racemate-based cocrystal was evaluated by means of X-ray diffraction, infrared spectroscopy, Raman, thermal analysis, and solubility experiments. The results were exhaustively compared with the first menthol-based pharmaceutical cocrystal, i.e., lidocaine:l-menthol, discovered in our group 12 years ago. Furthermore, the stable lidocaine/dl-menthol phase diagram has been screened, thoroughly evaluated, and compared to the enantiopure phase diagram. Thus, it has been proven that the racemic vs. enantiopure coformer leads to increased solubility and improved dissolution of lidocaine due to the low stable form induced by menthol molecular disorder in the lidocaine:dl-menthol cocrystal. To date, the 1:1 lidocaine:dl-menthol cocrystal is the third menthol-based pharmaceutical cocrystal, after the 1:1 lidocaine:l-menthol and the 1:2 lopinavir:l-menthol cocrystals reported in 2010 and 2022, respectively. Overall, this study shows promising potential for designing new materials with both improved characteristics and functional properties in the fields of pharmaceutical sciences and crystal engineering.

An ethnobotanical survey in the northern mountainous region of Vietnam identified four Elsholtzia species, E. blanda, E. ciliata, E. communis, and E. penduliflora, growing naturally above 1500 m and traditionally used by local ethnic communities to treat skin-related ailments. This study investigates their essential oil possible chemotypes, antimicrobial properties, and potential mechanisms of action through molecular docking. Essential oils obtained by steam distillation were analyzed using GC–MS. E. blanda (yield 1.17%) was characterized by high levels of 1,8-cineole (29.0%) and camphor (17.0%). E. ciliata (1.02%) represented a possible limonene-dominant chemotype (71.0%). E. communis (1.91%) contained an exceptionally high proportion of rosefuran oxide (86.2%), whereas E. penduliflora (0.91%) exhibited a pronounced 1,8-cineole chemotype (92.1%). All essential oils showed antimicrobial activity against Staphylococcus aureus (MSSA and MRSA), Escherichia coli, and Candida albicans, with MIC values ranging from 0.4% to 3.2%. Except for E. ciliata against C. albicans, MBC/MIC and MFC/MIC ratios ≤ 4 indicated predominantly bactericidal or fungicidal effects. Molecular docking further identified nine of twenty-eight detected constituents as strong binders to microbial target proteins. These findings expand current knowledge on possible chemotypic diversity within the genus, particularly the discovery of a high-altitude limonene chemotype in E. ciliata and the identification of E. penduliflora as a rich natural source of 1,8-cineole. The convergence of chemical, biological, and in silico evidence supports the ethnomedicinal relevance of Elsholtzia species and highlights their potential as candidates for developing natural antimicrobial agents.