Discipline of Pharmaceutical Technology, School of Pharmaceutical Sciences, Universiti Sains Malaysia , Minden, Malaysia.
Department of Pharmaceutics, UCL School of Pharmacy , London, UK.
Expert Opin Drug Deliv. 2020 Sep;17(9):1321-1334. doi: 10.1080/17425247.2020.1792440. Epub 2020 Jul 22.
Drug crystallization following application of transdermal and topical formulations may potentially compromise the delivery of drugs to the skin. This phenomenon was found to be limited to the superficial layers of the stratum corneum (~7 µm) in our recent reports and tape stripping of the skin samples was necessary. It remains a significant challenge to profile drug crystallization without damaging the skin samples.
This work reports the application of an X-ray microbeam via synchrotron SAXS/WAXS analysis to monitor drug crystallization in the skin, especially in the deeper skin layers. Confocal Raman spectroscopy (CRS) was employed to examine drug distribution in the skin to complement the detection of drug crystallization using SAXS/WAXS analysis.
Following application of saturated drug solutions (ibuprofen, diclofenac acid, and salts), CRS depth profiles confirmed that the drugs generally were delivered to a depth of ~15 - 20 µm in the skin. This was compared with the WAXS profiles that measured drug crystal diffraction at a depth of up to ~25 µm of the skin.
This study demonstrates the potential of synchrotron SAXS/WAXS analysis for profiling of drug crystallization in the deeper skin layers without pre-treatment for the skin samples. [Figure: see text].
经皮和局部制剂给药后药物结晶可能会影响药物向皮肤的传递。在我们最近的报告中发现，这种现象仅限于角质层的浅层（~7 µm），因此需要对皮肤样本进行胶带剥落。在不损伤皮肤样本的情况下对药物结晶进行分析仍然是一个重大挑战。
本研究报告了使用同步加速器 X 射线微束通过小角 X 射线散射/广角 X 射线散射分析来监测皮肤中的药物结晶，特别是在更深的皮肤层中。共焦拉曼光谱（CRS）用于检查药物在皮肤中的分布，以补充使用 SAXS/WAXS 分析检测药物结晶。
应用饱和药物溶液（布洛芬、双氯芬酸和盐）后，CRS 深度分布证实药物通常可输送至皮肤的深度约为 15-20 µm。这与 WAXS 分布进行了比较，WAXS 分布测量了皮肤深度高达 25 µm 处的药物晶体衍射。
本研究表明，同步加速器 SAXS/WAXS 分析有可能在不对皮肤样本进行预处理的情况下对深层皮肤层中的药物结晶进行分析。[图：见正文]。
