Melting Process of the Peritectic Mixture of Lidocaine and Ibuprofen Interpreted by Site Percolation Theory Model

• Published in: Journal of pharmaceutical sciences Vol. 106; no. 10; p. 3016
• Main Authors: Kataoka, Hikaru, Sakaki, Yoshinori, Komatsu, Kazushi, Shimada, Yohsuke, Goto, Satoru
• Format: Journal Article
• Language: English
• Published: United States 01-10-2017
• Subjects: Calorimetry, Differential Scanning - methods; Hot Temperature; Ibuprofen - chemistry; Kinetics; Lidocaine - chemistry; Magnetic Resonance Spectroscopy - methods; Spectroscopy, Fourier Transform Infrared - methods; Spectrum Analysis, Raman - methods; calorimetry (DSC); physical characterization; FTIR; interaction; NMR spectroscopy; Raman spectroscopy; kinetics; transition; solid state; thermal analysis
• ISSN: 1520-6017
• DOI: 10.1016/j.xphs.2017.04.010

Eutectic mixtures are often used in the design and delivery of drugs. In this study, we examined the peritectic mixture of lidocaine (LDC) and ibuprofen (IBP) using differential scanning calorimetry, Raman spectroscopy, and microscopy. The obtained phase diagram showed that as the mixture was heated, first LDC melted at 293 K, then IBP dissolved in the liquefied LDC at 310 K, and finally all remaining crystals melted. In the
H NMR spectra, the signals of the carboxyl group in IBP and amide or amine group in LDC shifted to the low magnetic field in the IBP/LDC mixtures, because of the intermolecular interaction between these moieties. Using FTIR spectroscopy, the kinetic "reaction" order of the melting process in the mixtures with excess LDC, equimolar, and excess IBP was determined to be +1/2, -1/2, and 0, respectively. The 2 contacts between the liquidus line and the higher melting line at 310 K at IBP molar fractions of 1/3 and of 2/3 were explained on the basis of the site percolation theory.