Characterization and Comparison of Lidocaine-Tetracaine and Lidocaine-Camphor Eutectic Mixtures Based on Their Crystallization and Hydrogen-Bonding Abilities

Abstract

Abstract. Eutectic mixtures formed between active pharmaceutical ingredients and/or excipients provide vast scope for pharmaceutical applications. This study aimed at the exploration of the crystallization abilities of two eutectic mixtures (EM) i.e., lidocaine-tetracaine and lidocaine-camphor (1:1 w/w). Thermogravimetric analysis (TGA) for degradation behavior whereas modulated temperature differential scanning calorimetry (MTDSC) set in first heating, cooling, and second heating cycles, was used to qualitatively analyze the complex exothermic and endothermic thermal transitions. Raman microspectroscopy characterized vibrational information specific to chemical bonds. Prepared EMs were left at room temperature for 24 h to visually examine their crystallization potentials. The degradation of lidocaine, tetracaine, camphor, lidocaine-tetracaine EM, and lidocaine-camphor EM began at 196.56, 163.82, 76.86, 146.01, and 42.72°C, respectively, which indicated that eutectic mixtures are less thermostable compared to their individual components. The MTDSC showed crystallization peaks for lidocaine, tetracaine, and camphor at 31.86, 29.36, and 174.02°C, respectively (n=3). When studying the eutectic mixture, no crystallization peak was observed in the lidocaine-tetracaine EM, but a lidocaine-camphor EM crystallization peak was present at 18.81°C. Crystallization occurred in lidocaine-camphor EM after being kept at room temperature for 24 h, but not in lidocaine-tetracaine EM. Certain peak shifts were observed in Raman spectra which indicated possible interactions of eutectic mixture components, when a eutectic mixture was formed. We found that if the components forming a eutectic mixture have crystallization peaks close to each other and have sufficient hydrogen-bonding capability, then their eutectic mixture is least likely to crystallize out (as seen in lidocaine-tetracaine EM) or vice versa (lidocainecamphor EM).

Drug Solubility Enhancement through the Preparation of Multicomponent Organic Materials: Eutectics of Lovastatin with Carboxylic Acids

“…One of the requirements for eutectic mixture formation is that the components forming the mixture should have moieties that can interact to form noncovalent interactions [4], with a major presence of electrostatic interactions [42]. In the case of LOV and the selected carboxylic acids (Figure 1), the main interaction should occur between the carbonyl and hydroxyl groups present in both LOV and the carboxylic acids used.…”

“…Eutectic mixtures are multicomponent organic materials formed by two or more crystalline solids that are immiscible in the solid state and miscible in the liquid state [1,2]. Their formation occurs via noncovalent forces [3,4], mainly hydrogen bonding, ionic and van der Waals forces, and aromatic interactions [4]. In general, the melting temperature of the eutectic is lower than the melting temperatures of their parent components [5].…”

Deep Eutectic Solvents and Pharmaceuticals

“…The study of the anti- Most API-DES reported to date exhibit melting temperatures near or below the human body's temperature and usually envisage topical and oral administration [18,83,84]. Initially, the majority of these liquid forms were designed for transdermal purposes and included permeation enhancers, such as terpenes and fatty acids [19,85,86]. In 1998, Stott and coworkers [83] reported a series of API-DES based on ibuprofen and different permeation enhancers, such as L-menthol, L-menthone thymol, D-limonene, 1,8-cineole and p-cymene.…”

Deep Eutectic Solvents as Active Pharmaceutical Ingredient Delivery Systems in the Treatment of Metabolic Related Diseases

“…APIs, such as menthol, ibuprofen, lidocaine, itraconazole, cannabidiol and testosterone, were involved in the formation of API-based DESs, which maintained in the therapeutic effect of the APIs (Aroso et al, 2015;Aroso et al, 2016;Cordeiro et al, 2017;Duarte et al, 2017;Gala et al, 2015;Kaplun-Frischoff & Touitou, 1997;Lodzki et al, 2003;Morimoto et al, 2000;Park et al, 2012;Silva et al, 2019;Stott et al, 1998;Wang et al, 2017;Woolfson et al, 2000) (Figure 1, Table 1). Silva et al constructed hydrophobic DESs based on menthol and saturated fatty acids with different chain lengths, including stearic acid, myristic acid and lauric acid, and evaluated the toxicity and antibacterial activity of these DESs to human immortal keratinocyte line (HaCaT) cells (Silva et al, 2019).…”