Discipline of Pharmaceutical Technology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800, Minden, Penang, Malaysia; Department of Pharmaceutics, UCL School of Pharmacy, 29-39 Brunswick Square, London, WC1N 1AX, United Kingdom.
Department of Medical Physics and Biomedical Engineering, University College London, Gower Street, London, WC1E 6BT, United Kingdom.
Micron. 2021 Jun;145:103045. doi: 10.1016/j.micron.2021.103045. Epub 2021 Mar 2.
Drug crystallisation in the skin is recognised as a significant problem in topical and transdermal drug delivery. Our recent investigations provided new evidence of drug crystallisation in the skin, however, confirming the precise location of crystals remains challenging. Of note, most approaches used have required disruption of the membrane by tape stripping, with crystal detection limited to the superficial skin layers. Hence, a non-destructive method for complete spatial resolution of crystallised drug in skin is still lacking. In this communication, we report the application of X-ray micro-computed tomography (microCT) to examine drug crystallisation in mammalian skin ex vivo. Permeation studies of a saturated solution of diclofenac sodium were conducted in porcine skin; subsequently, tissue samples were scanned using microCT to generate 2D and 3D maps. A layer of drug crystals was observed on the skin surface; microCT maps also confirmed the distribution of drug crystals up to a skin depth of 0.2 - 0.3 mm. MicroCT also allowed the identification of drug crystallisation as a distinct and confirmed event in the skin and as an extension from drug crystals formed on the skin. These preliminary results confirm the potential of microCT to study this important phenomenon in topical and transdermal drug delivery.
药物在皮肤中的结晶被认为是局部和经皮给药的一个重大问题。我们最近的研究提供了药物在皮肤中结晶的新证据，但确认晶体的确切位置仍然具有挑战性。值得注意的是，大多数使用的方法都需要通过胶带剥离来破坏膜，晶体检测仅限于皮肤的浅层。因此，仍然缺乏一种用于完整空间分辨率的结晶药物在皮肤中的非破坏性方法。在本通讯中，我们报告了应用 X 射线微计算机断层扫描（microCT）来检查哺乳动物皮肤的药物结晶。在猪皮上进行了双氯芬酸钠饱和溶液的渗透研究；随后，使用 microCT 对组织样本进行扫描，以生成 2D 和 3D 图谱。在皮肤表面观察到一层药物晶体；microCT 图谱还证实了药物晶体的分布深度可达 0.2-0.3 毫米。microCT 还可以识别药物结晶作为皮肤中一个独特且已确认的事件，以及从皮肤表面形成的药物晶体的延伸。这些初步结果证实了 microCT 在研究局部和经皮药物输送中这一重要现象的潜力。
