UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, UK.
London Metropolitan University, 166-220 Holloway Road, London N7 8DB, UK.
Int J Pharm. 2020 Apr 15;579:119137. doi: 10.1016/j.ijpharm.2020.119137. Epub 2020 Feb 11.
Niacinamide (NIA) has been widely used in cosmetic and personal care formulations for several skin conditions. Permeation of topical NIA has been confirmed in a number of studies under infinite dose conditions. However, there is limited information in the literature regarding permeation of NIA following application of topical formulations in amounts that reflect the real-life use of such products by consumers. The aim of the present work was therefore to investigate skin delivery of NIA from single solvent systems in porcine skin under finite dose conditions. A secondary aim was to probe the processes underlying the previously reported low recovery of NIA following in vitro permeation and mass balance studies. The solubility and stability of NIA in various single solvent systems was examined. The solvents investigated included Transcutol® P (TC), propylene glycol (PG), 1-2 hexanediol (HEX), 1-2 pentanediol (1-2P), 1-5 pentanediol (1-5P), 1-3 butanediol (1-3B), glycerol (GLY) and dimethyl isosorbide (DMI). Skin permeation and deposition of the molecule was investigated in full thickness porcine skin in vitro finite dose Franz-type diffusion experiments followed by mass balance studies. Stability of NIA for 72 h in the solvents was confirmed. The solubility of NIA in the solvents ranged from 82.9 ± 0.8 to 311.9 ± 4.5 mg/mL. TC delivered the highest percentage permeation of NIA at 24 h, 32.6 ± 12.1% of the applied dose. Low total recovery of NIA after mass balance studies was observed for some vehicles, with values ranging from 55.2 ± 12.8% to 106.3 ± 2.3%. This reflected the formation of a number of NIA degradation by-products in the receptor phase during the permeation studies. Identification of other vehicles for synergistic enhancement of NIA skin delivery will be the subject of future work.
烟酰胺（NIA）已广泛应用于多种皮肤状况的化妆品和个人护理制剂中。已有多项研究证实，在无限剂量条件下，局部 NIA 能够渗透皮肤。然而，关于在消费者实际使用此类产品的剂量下，局部制剂应用后 NIA 的渗透情况，文献中仅有有限的信息。因此，本研究旨在研究有限剂量条件下，猪皮中单溶剂体系中 NIA 的经皮传递。本研究的次要目的是探究之前报道的体外渗透和质量平衡研究中 NIA 回收率低的原因。考察了 NIA 在各种单溶剂体系中的溶解度和稳定性。所研究的溶剂包括 Transcutol® P（TC）、丙二醇（PG）、1,2-己二醇（HEX）、1,2-戊二醇（1-2P）、1,5-戊二醇（1-5P）、1,3-丁二醇（1-3B）、甘油（GLY）和二甲基异山梨醇（DMI）。采用体外有限剂量Franz 型扩散实验，随后进行质量平衡研究，研究了分子在全厚猪皮中的渗透和沉积情况。在溶剂中 72 h 内确认了 NIA 的稳定性。NIA 在溶剂中的溶解度范围为 82.9±0.8 至 311.9±4.5 mg/mL。24 h 时，TC 输送的 NIA 透皮率最高，为施加剂量的 32.6±12.1%。一些载体的质量平衡研究后总回收率较低，范围为 55.2±12.8%至 106.3±2.3%。这反映了在渗透研究过程中，受体相中形成了许多 NIA 降解副产物。未来的工作将确定其他用于协同增强 NIA 皮肤传递的载体。
