Research & Innovation, Seppic, 127 Chemin de la Poudrerie, 81100 Castres, France.
Int J Mol Sci. 2024 Jul 6;25(13):7432. doi: 10.3390/ijms25137432.
Skin penetration of an active pharmaceutical ingredient is key to developing topical drugs. This penetration can be adjusted for greater efficacy and/or safety through the selection of dosage form. Two emerging dosage forms, cream-gel and gel-in-oil emulsion, were tested for their ability to deliver diclofenac into the skin, with the target of maximising skin retention while limiting systemic exposure. Prototypes with varying amounts of solvents and emollients were formulated and evaluated by in vitro penetration testing on human skin. Cream-gel formulas showed better skin penetration than the emulgel benchmark drug even without added solvent, while gel-in-oil emulsions resulted in reduced diffusion of the active into the receptor fluid. Adding propylene glycol and diethylene glycol monoethyl ether as penetration enhancers resulted in different diclofenac penetration profiles depending on the dosage form and whether they were added to the disperse or continuous phase. Rheological characterisation of the prototypes revealed similar profiles of cream-gel and emulgel benchmark, whereas gel-in-oil emulsion demonstrated flow characteristics suitable for massaging product into the skin. This study underlined the potential of cream-gel and gel-in-oil emulsions for adjusting active penetration into the skin, broadening the range of choices available to topical formulation scientists.
药物活性成分经皮渗透是开发局部用药物的关键。通过选择剂型，可以调整这种渗透以提高疗效和/或安全性。本文测试了两种新兴的剂型——乳膏-凝胶和油包水型乳剂凝胶，以考察其将双氯芬酸递送至皮肤的能力，目标是在限制全身暴露的同时最大限度地增加皮肤滞留。通过对人体皮肤进行体外渗透试验，对具有不同溶剂和赋形剂含量的原型进行了配方和评价。即使没有添加溶剂，乳膏-凝胶配方的皮肤渗透能力也优于乳剂凝胶对照药物，而油包水型乳剂凝胶则导致活性物质向接受液中的扩散减少。添加丙二醇和二乙二醇单乙基醚作为渗透增强剂会导致双氯芬酸的渗透特性因剂型而异，具体取决于它们是添加到分散相还是连续相。原型的流变学特性表明，乳膏-凝胶和乳剂凝胶对照的特性相似，而油包水型乳剂凝胶则表现出适合按摩产品进入皮肤的流动特性。本研究强调了乳膏-凝胶和油包水型乳剂凝胶在调节药物活性成分经皮渗透方面的潜力，为局部制剂科学家提供了更多的选择。
