Molecular Complex Consisting of Two Typical External Medicines: Intermolecular Interaction between Indomethacin and Lidocaine

The molecular complex formed between indomethacin (IDM) and lidocaine (LDC), which are typical external medicines, was studied. A thermal analysis, microscopic study and phase solubility technique suggested intermolecular interaction between IDM and LDC. The phase solubility profiles with IDM and LDC were classified as A(L)-type, indicating the formation of a 1 : 1 stoichiometric molecular complex. The apparent stability constant (K(S)), calculated from the slope and the intercept, was 4478.9 M(-1). A molecular ion peak was detected at 592.2 (m/z) from fast-atom bombardment-MS measurements, which was in accordance with the sum of the molecular weight for IDM (M(W): 357.81) and LDC (M(W): 234.38). The changes of IR spectra in the C=O stretching region showed that each intact hydrogen bond network was collapsed in the IDM-LDC system and strong interaction between IDM and LDC formed after their kneading. From the (1)H-NMR analyses, it was estimated that the dominant interactive site was the IDM carboxylic acid group which associated with the LDC diethyl amino group non-covalently.