Drug crystallization on and in the skin has been reported following application of topical or transdermal formulations. This study explored novel probe-based approaches including localized nanothermal analysis (nano-TA) and photothermal microspectroscopy (PTMS) to investigate and locate drug crystals in the stratum corneum (SC) of porcine skin following application of simple ibuprofen (IBU) formulations. We also conducted in vitro skin permeation studies and tape stripping. The detection of drug crystals in the SC on tape strips was confirmed using localized nano-TA, based on the melting temperature of IBU. The melting of IBU was also evident as indicated by a double transition and confirmed the presence of drug crystals in the SC. The single point scans of PTMS on the tape strips allowed collection of the photothermal FTIR spectra of IBU, confirming the existence of drug crystals in the skin. The combined methods also indicated that drug crystallized in the SC at a depth of ∼4–7 μm. Future studies will examine the potential of these techniques to probe crystallization of other commonly used actives in topical and transdermal formulations.

中文翻译：

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使用局部纳米热分析和光热显微技术监测经皮穿刺中的药物结晶

在局部或透皮制剂的应用后，已经报道了药物在皮肤上和皮肤中的结晶。这项研究探索了基于探针的新颖方法，包括局部纳米热分析（nano-TA）和光热显微光谱（PTMS），以研究和定位简单布洛芬（IBU）配方后猪皮肤角质层（SC）中的药物晶体。我们还进行了体外皮肤渗透研究和胶带剥离。根据IBU的熔化温度，使用局部纳米TA证实了在条带上SC中药物晶体的检测。IBU的熔化也很明显，这是由双重转变所表明的，并证实了SC中存在药物晶体。在条带上进行PTMS的单点扫描可以收集IBU的光热FTIR光谱，确认皮肤中存在药物晶体。组合方法还表明，药物在SC中结晶的深度约为4-7μm。未来的研究将研究这些技术在局部和透皮制剂中探测其他常用活性成分结晶的潜力。