Phase Diagram and Aqueous Solubility of the Lidocaine-Prilocaine Binary System

Brodin, Arne; Nyqvist-Mayer, Adela A.; Wadsten, T.; Forslund, B.; Broberg, F

doi:10.1002/jps.2600730413

Cited by 93 publications

(61 citation statements)

References 6 publications

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“…In contrast, liquid drug formulations are much less common, and are usually based on eutectic mixtures. [38,39] However, problems associated with the solid form of many drugs have been consistently reported; issues include polymorphic conversion, low solubility, low bioavailability for crystalline solids, and the tendency of amorphous forms to spontaneously crystallize. For these reasons, and also due to considerable financial interests brought about by legal ramifications, screening for new drug forms, including salts, solvates, and cocrystals is a continuous pursuit.…”

Section: Ionic Pharmaceuticals and The Polymorphism Problemmentioning

confidence: 99%

Ionic Liquids as Active Pharmaceutical Ingredients

et al. 2011

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Ionic liquids (ILs) are ionic compounds that possess a melting temperature below 100 °C. Their physical and chemical properties are attractive for various applications. Several organic materials that are now classified as ionic liquids were described as far back as the mid-19th century. The search for new and different ILs has led to the progressive development and application of three generations of ILs: 1) The focus of the first generation was mainly on their unique intrinsic physical and chemical properties, such as density, viscosity, conductivity, solubility, and high thermal and chemical stability. 2) The second generation of ILs offered the potential to tune some of these physical and chemical properties, allowing the formation of "task-specific ionic liquids" which can have application as lubricants, energetic materials (in the case of selective separation and extraction processes), and as more environmentally friendly (greener) reaction solvents, among others. 3) The third and most recent generation of ILs involve active pharmaceutical ingredients (API), which are being used to produce ILs with biological activity. Herein we summarize recent developments in the area of third-generation ionic liquids that are being used as APIs, with a particular focus on efforts to overcome current hurdles encountered by APIs. We also offer some innovative solutions in new medical treatment and delivery options.

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Section: Ionic Pharmaceuticals and The Polymorphism Problemmentioning

confidence: 99%

Ionic Liquids as Active Pharmaceutical Ingredients

et al. 2011

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“…DOI: 10.3109/10717544.2014.923067 (eutectic mixture) was obtained. The eutectic mixture, so obtained, was allowed to equilibrate at room temperature (21-25 C) for 24 h prior to use (Brodin et al, 1984). For the development of MEs, IPM was selected as the oil phase as it was completely miscible with EMLP.…”

Section: Preparation Of Emlp and Screening Of Components For Mesmentioning

confidence: 99%

Phospholipid microemulsion-based hydrogel for enhanced topical delivery of lidocaine and prilocaine: QbD-based development and evaluation

et al. 2014

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Topical delivery of local anesthetics has been an area of interest for researchers considering the barrier properties of skin and unfavorable physicochemical properties of drugs. In the present study, efforts have been made to modify the in vivo efficacy of eutectic mixture of lidocaine and prilocaine by exploiting the phospholipid modified microemulsion based delivery systems. The strategic QbD (D-optimal mixture design) enabled systematic optimization approach, after having obtained the isotropic area of interest by ternary phase diagram, has resulted into the system with most desirable attributes. Latter include nano-scale, globular structures with an average size of 40.6 nm, as characterized by TEM and DLS. The optimized microemulsion systems in gel dosage forms revealed the better permeability over commercial cream (CC) through abdominal rat skin. Enhancement in the flux from M OPT-NMP gel was 3.22-folds for prilocaine and 4.94-folds for lidocaine, in comparison to that of CC. This enhanced skin permeability is very well reflected in the in vivo studies, wherein intensity and duration of action was augmented significantly. The skin compliance of the optimized formulation was revealed in histopathological studies. The overall benefit relating to efficacy and safety-compliance could be correlated to the uniqueness of the carriers, composed of phospholipids and other components. Hence, the developed phospholipid-microemulsion based gel formulation has been proposed as more useful alternative for the topical delivery of lidocaine and prilocaine.

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“…However, owing to the toxic side effects of cocaine and the caustic properties of phenol, this mixture was seldom used. Later on, an emulsion containing equal amounts of lidocaine and prilocaine, called EMLA (eutectic mixture of local anesthetics) cream, was used for topical anesthesia (11)(12)(13). In a study, the EMLA cream was found to be more effective compared to a bonain mixture for eardrum anesthesia (14).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2014

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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).

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Phase Diagram and Aqueous Solubility of the Lidocaine-Prilocaine Binary System

Cited by 93 publications

References 6 publications

Ionic Liquids as Active Pharmaceutical Ingredients

Ionic Liquids as Active Pharmaceutical Ingredients

Phospholipid microemulsion-based hydrogel for enhanced topical delivery of lidocaine and prilocaine: QbD-based development and evaluation

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

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