Bhatt V, Pillai R
Dow Pharmaceutical Sciences (A Division of Valeant Pharmaceutical North America LLC), Petaluma, California.
J Pharm Sci. 2015 Jul;104(7):2177-82. doi: 10.1002/jps.24459. Epub 2015 May 4.
Transungual drug delivery of antifungals is considered highly desirable to treat common nail disorders such as onychomycosis, due to localized effects, and improved adherence resulting from minimal systemic adverse events. However, the development of effective topical therapies has been hampered by poor nail penetration. An effective topical antifungal must permeate through, and under the dense keratinized nail plate to the site of infection in the nail bed and nail matrix. We present here the formulation development program to provide effective transungual and subungual delivery of efinaconazole, the first topical broad spectrum triazole specifically developed for onychomycosis treatment. We discuss the important aspects encompassing the formulation development program for efinaconazole topical solution, 10%, focusing on its solubility in a number of solvents, in vitro penetration through the nail, and in vivo efficacy. Efinaconazole topical solution, 10% is a stable, non-lacquer, antifungal with a unique combination of ingredients added to an alcohol-based formulation to provide low surface tension and good wetting properties. This low surface tension is believed to affect effective transungual delivery of efinaconazole and believed to provide a dual mode of delivery by accessing the nail bed by wicking into the space between the nail and nail plate.
由于局部作用以及全身不良事件极少所带来的依从性提高，抗真菌药物的经甲给药被认为是治疗常见指甲疾病（如甲癣）的理想方式。然而，有效的局部治疗方法的开发一直受到指甲渗透率低的阻碍。一种有效的局部抗真菌药物必须穿透致密的角化指甲板并到达甲床和甲母质的感染部位。我们在此展示了一个制剂开发项目，以实现艾氟康唑的有效经甲和甲下给药，艾氟康唑是首个专门为治疗甲癣而开发的局部广谱三唑类药物。我们讨论了涵盖10% 艾氟康唑局部溶液制剂开发项目的重要方面，重点关注其在多种溶剂中的溶解度、体外经指甲渗透率以及体内疗效。10% 艾氟康唑局部溶液是一种稳定的非漆剂抗真菌药物，在基于酒精的制剂中添加了独特的成分组合，以提供低表面张力和良好的润湿性。这种低表面张力被认为会影响艾氟康唑的有效经甲给药，并被认为通过芯吸进入指甲与指甲板之间的间隙到达甲床，从而提供双重给药模式。
