Abstract：
The study aimed to create a low loading, high retention, easier to apply O/W mometasone furoate (MF) cream using a chemical enhancer (CE) approach to provide more options for patients with atopic dermatitis (AD) and to investigate molecular mechanisms of its increased release and retention. A Box-Behnken design determined the optimal formulation based on stability and in vitro skin retention. Evaluations included appearance, rheological properties, irritation, in vivo tissue distribution and pharmacodynamics. Molecular mechanisms of enhanced release were studied using high-speed centrifugation, molecular dynamics and rheology. The interaction between the CE, MF and skin was studied by tape stripping, CLSM, ATR-FTIR and SAXS. The formulation was optimized to contain 0.05% MF and used 10% polyglyceryl-3 oleate (POCC) as the CE. There was no significant difference from Elocon® cream in in vivo retention and pharmacodynamics but increased in vivo retention by 3.14-fold and in vitro release by 1.77-fold compared to the basic formulation. POCC reduced oil phase cohesive energy density, enhancing drug mobility and release. It disrupted skin lipid phases, aiding drug entry and formed hydrogen bonds, prolonging retention. This study highlights POCC as a CE in the cream, offering insights for semi-solid formulation development.
摘要：
这项研究旨在创造一个低负荷，高保留,使用化学增强剂（CE）方法更容易应用O/W糠酸莫米松（MF）乳膏，为特应性皮炎（AD）患者提供更多选择，并研究其释放和保留增加的分子机制。Box-Behnken设计基于稳定性和体外皮肤保留确定了最佳配方。评估包括外观，流变性能,刺激,体内组织分布和药效学。使用高速离心法研究了增强释放的分子机制，分子动力学和流变学。CE之间的相互作用，通过胶带剥离研究了MF和皮肤，CLSM,ATR-FTIR和SAXS。优化配方以含有0.05%MF,并使用10%聚甘油-3油酸酯(POCC)作为CE。与Elocon®乳膏在体内保留和药效学方面没有显著差异,但与基础制剂相比,体内保留增加3.14倍,体外释放增加1.77倍。POCC降低了油相内聚能密度，增强药物的流动性和释放。它破坏了皮肤脂质相，帮助药物进入并形成氢键，延长保留时间。这项研究强调了POCC作为奶油中的CE，为半固体制剂的开发提供见解。
