EAD Physico-chimie Industrielle du Médicament (EA 4066), Faculté de Pharmacie, Université Paris Descartes, 4, Avenue de l'Observatoire, 75006 Paris, France.
Mol Pharm. 2013 Apr 1;10(4):1332-9. doi: 10.1021/mp300542k. Epub 2013 Mar 18.
EMLA cream, a "eutectic mixture of local anesthetics", was developed in the early 1980s by Astra Pharmaceutical Production. The mixture of anesthetics containing lidocaine, prilocaine, and water is liquid at room temperature, which is partly due to the eutectic equilibrium between prilocaine and lidocaine at 293 K, as was clear from the start. However, the full thermodynamic background for the stability of the liquid and its emulsion-like appearance has never been elucidated. In the present study of the binary system prilocaine-water, a region of liquid-liquid demixing has been observed, linked to a monotectic equilibrium at 302.4 K. It results in a prilocaine-rich liquid containing approximately 0.7 mol fraction of anesthetic. Similar behavior has been reported for the binary system lidocaine-water (Céolin, R.; et al. J. Pharm. Sci. 2010, 99 (6), 2756-2765). In the ternary mixture, the combination of the monotectic equilibrium and the above-mentioned eutectic equilibrium between prilocaine and lidocaine results in an anesthetic-rich liquid that remains stable below room temperature. This liquid forms an emulsion-like mixture in the presence of an aqueous solution saturated with anesthetics. Physical properties and the crystal structure of prilocaine are also reported.
EMLA 乳膏，一种“局部麻醉剂的共晶混合物”，由 Astra 制药公司于 20 世纪 80 年代早期开发。这种包含利多卡因、丙胺卡因和水的麻醉剂混合物在室温下呈液态，这在一开始就很明显，部分原因是丙胺卡因和利多卡因在 293 K 时的共晶平衡。然而，对于液体的稳定性及其乳状外观的全部热力学背景从未得到阐明。在本研究中，观察到丙胺卡因-水二元体系存在液-液分相区域，与 302.4 K 时的单变平衡有关。这导致了一种富含丙胺卡因的液体，其中含有约 0.7 摩尔分数的麻醉剂。对于利多卡因-水二元体系（Céolin，R.；等人。J. Pharm. Sci. 2010, 99 (6), 2756-2765），也报道了类似的行为。在三元混合物中，单变平衡和丙胺卡因与利多卡因之间的上述共晶平衡的结合导致一种在室温以下仍保持稳定的富含麻醉剂的液体。这种液体在含有麻醉剂饱和水溶液的情况下形成乳状混合物。还报告了丙胺卡因的物理性质和晶体结构。
