Freie Universität Berlin, Institute of Pharmacy, Germany.
Freie Universität Berlin, Institute of Pharmacy, Germany.
Int J Pharm. 2019 Jan 30;555:314-321. doi: 10.1016/j.ijpharm.2018.11.018. Epub 2018 Nov 13.
Dermally applied poorly soluble actives whether in cosmetics or pharmaceuticals show insufficient skin penetration. Especially actives being insoluble in both phases of dermal vehicles, i.e. water and oil have no or less real effect. An approach to overcome this obstacle is the use of amorphous actives instead of the crystalline ones. The higher saturation solubility creates an increased concentration gradient between the formulation and skin. Thus, the diffusive flux into the skin is improved. However, the amorphous state of actives is highly labile, and the durability of such formulations would be too short for a marketable product. smartPearls is a novel technology efficiently long-term stabilize the amorphous state. They consist of µm sized particles with mesopores (e.g. silica: SYLOID, AEROPERL, Neusilin), in which the active can be loaded and preserved in amorphous state. Due to the tightness of the pores, not enough space is given for re-crystallization. In this work, the skin penetration of poorly soluble actives loaded in smartPearls is compared to the present "gold standards" in dermal delivery, e.g. amorphous microparticles, amorphous nanoparticles and nanocrystals. The performance was at least similar or even better than the gold standards, explainable by the increased saturation solubility of active due to a) amorphous state and b) nanostructure inside the µm-sized particles. Sedimentation investigations showed, that the physical stabilization of very dense smartPearls in semi-solid vehicles is possible by viscoelastic repulsion. Also, the technical, regulatory and marketing aspects for the use of smartPearls technology in products are discussed, e.g. status of excipients used, and advantages of not being a nanoparticle, but being as efficient as them. Overall, smartPearls proved to be a promising dermal delivery technology for poorly soluble actives with a high market potential.
经皮应用的脂溶性差的活性物质，无论是在化妆品还是药物中，都显示出皮肤渗透不足。特别是那些在皮肤载体的水相和油相都不溶的活性物质，几乎没有或没有实际效果。克服这一障碍的一种方法是使用无定形活性物质代替结晶活性物质。较高的饱和溶解度在配方和皮肤之间产生了更大的浓度梯度。因此，进入皮肤的扩散通量得到了改善。然而，活性物质的无定形状态非常不稳定，这种配方的耐久性对于可销售的产品来说太短了。smartPearls 是一种新颖的技术，可以有效地长期稳定无定形状态。它们由微米大小的颗粒组成，具有中孔（例如二氧化硅：SYLOID、AEROPERL、Neusilin），其中活性物质可以被负载并以无定形状态保存。由于孔的紧密性，没有足够的空间重新结晶。在这项工作中，将负载在 smartPearls 中的脂溶性差的活性物质的皮肤渗透与皮肤传递的现有“金标准”进行了比较，例如无定形微粒、无定形纳米颗粒和纳米晶体。其性能至少与金标准相似，甚至更好，这可以归因于活性物质的溶解度增加，原因是 a）无定形状态和 b）微米级颗粒内的纳米结构。沉降研究表明，通过粘弹性斥力可以实现非常致密的 smartPearls 在半固体载体中的物理稳定。还讨论了在产品中使用 smartPearls 技术的技术、监管和营销方面，例如所用辅料的状况，以及作为纳米颗粒的优势，而不是像它们一样有效。总的来说，smartPearls 被证明是一种有前途的用于脂溶性差的活性物质的透皮传递技术，具有很高的市场潜力。
