Background

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 in situ without damaging the skin samples.

Methods

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.

Results

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.

Conclusion

This study demonstrates the potential of synchrotron SAXS/WAXS analysis for profiling of drug crystallization in situ in the deeper skin layers without pre-treatment for the skin samples.

中文翻译：

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皮肤中药物结晶的分析。

背景

透皮和局部制剂应用后的药物结晶可能会损害药物向皮肤的输送。在我们最近的报道中，发现这种现象仅限于角质层的表层（〜7 µm），并且需要剥离皮肤样本。在不损害皮肤样品的情况下，原位分析药物结晶仍然是一项重大挑战。

方法

这项工作报告了通过同步加速器SAXS / WAXS分析在X射线微束中的应用，以监测皮肤（尤其是深层皮肤）中的药物结晶。共焦拉曼光谱法（CRS）用于检查药物在皮肤中的分布，以补充使用SAXS / WAXS分析进行药物结晶的检测。

结果

在使用饱和药物溶液（布洛芬，双氯芬酸和盐）后，CRS的深度曲线证实，药物通常在皮肤中的递送深度约为15至20 µm。将此结果与WAXS曲线进行了比较，该曲线在皮肤的最大〜25 µm深度处测量了药物晶体的衍射。

结论

这项研究证明了同步加速器SAXS / WAXS分析在不对皮肤样品进行预处理的情况下，在更深的皮肤层中原位分析药物结晶的潜力。