Franz Cell Diffusion Testing and Quantitative Confocal Raman Spectroscopy: In Vitro-In Vivo Correlation.
Franz Cell Diffusion Testing and Quantitative Confocal Raman Spectroscopy: In Vitro-In Vivo Correlation.
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DOI：
10.3390/pharmaceutics12090887
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发表时间：
2020-09-18
期刊：
影响因子：
5.4
通讯作者：
Lane ME
中科院分区：
文献类型：
--
作者：
Iliopoulos F;Caspers PJ;Puppels GJ;Lane ME
之前，我们报道了使用共焦拉曼光谱（CRS）来研究活性物质和赋形剂的局部递送。我们还将 CRS 的结果与人体皮肤体外扩散研究的结果相关联。然而，到目前为止，CRS 仅用作确定皮肤分子吸收的半定量方法，结果表示为信号强度的任意单位。显然，这对使用 CRS 确定皮肤递送并评估局部制剂的药物生物利用度和生物等效性提出了挑战。在目前的工作中，使用传统的 Franz 池在体外研究了烟酰胺 (NIA) 在人体皮肤中从各种制剂中的渗透性，并在有限剂量条件下使用定量 CRS 方法在体内研究了烟酰胺 (NIA) 在人体皮肤中的渗透性。选择 NIA 是因为它多年来在制药和个人护理配方中广泛使用。这是第一个比较这些方法的完全定量研究。所研究的车辆是纯 Transcutol® P (TC)；丙二醇(PG)与丙二醇单月桂酸酯(PGML)的二元组合；以及PG、PGML和肉豆蔻酸异丙酯(IPM)的三元混合物。选择这些溶剂是为了涵盖一系列物理化学性质。所有体外和体内制剂的 NIA 渗透性都很明显。载体 PG:PGML 和 PG:PGML:IPM 在 24 小时体外在皮肤上的递送量相当（100.3–106.7 µg/cm2，p > 0.05），明显高于 TC 的量（1.3 µg/cm2，p < 0.05）。将体外渗透的 NIA 累积量与 CRS 测量的皮肤 2 μm 处的 NIA 量进行线性回归，发现良好的体外体内相关性 (R2 = 0.98)。体外NIA累积渗透量与体内单位表面积(μg/cm2)渗透角质层(SC)的NIA总量之间也观察到了很好的相关性，Pearson相关系数(R2)为0.94。研究结果支持使用 CRS 来定量测量体内输送到皮肤的活性物质。未来的研究将侧重于通过调查更广泛的车辆中不同活性物质的输送来探索该方法的再现性和可靠性。此外，定量 CRS 将作为评估外用制剂生物等效性的方法进行进一步评估。
Previously, we reported the use of Confocal Raman Spectroscopy (CRS) to investigate the topical delivery of actives and excipients. We have also correlated the results from CRS with findings from in vitro diffusion studies in human skin. However, until now CRS has only been used as a semi-quantitative method of determining the skin uptake of molecules, with results expressed as arbitrary units of signal intensity. Clearly, this posed challenges for using CRS to determine skin delivery and to assess the drug bioavailability and bioequivalence of topical formulations. In the present work, the permeation of niacinamide (NIA) from various formulations in human skin was studied in vitro using conventional Franz cells and in vivo using a quantitative CRS method under finite dose conditions. The selection of NIA was based on its wide use in pharmaceutical and personal care formulations for many years. This is the first fully quantitative study to compare these methods. The vehicles investigated were neat Transcutol® P (TC); binary combinations of propylene glycol (PG) with propylene glycol monolaurate (PGML); and ternary mixtures of PG, PGML, and isopropyl myristate (IPM). These solvents were selected to encompass a range of physicochemical properties. NIA permeation was evident from all formulations in vitro and in vivo. The vehicles PG:PGML and PG:PGML:IPM delivered comparable amounts across the skin in vitro at 24 h (100.3–106.7 µg/cm2, p > 0.05) that were significantly higher compared with those of TC (1.3 µg/cm2, p < 0.05). An excellent in vitro in vivo correlation (R2 = 0.98) was found following the linear regression of the cumulative amounts of NIA permeated in vitro and the amounts of NIA at 2 μm in the skin measured with CRS. A very good correlation between the cumulative permeation of NIA in vitro and the total amount of NIA that penetrated the stratum corneum (SC) per unit of surface area (μg/cm2) in vivo was also observed, with a Pearson correlation coefficient (R2) of 0.94. The findings support the use of CRS for the quantitative measurement of actives delivered to the skin in vivo. Future studies will focus on exploring the reproducibility and reliability of the method by investigating the delivery of different actives from a wider range of vehicles. Additionally, quantitative CRS will be evaluated further as a method for assessing the bioequivalence of topical formulations.
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影响因子：
6.5
作者：
Benfeldt, Eva;Hansen, Steen H.;Shah, Vinod P.
通讯作者：
Shah, Vinod P.
影响因子：
3.7
作者：
Caspers, PJ;Williams, AC;Puppels, GJ
通讯作者：
Puppels, GJ
影响因子：
3.4
作者：
Eichner, Adina;Stahlberg, Soeren;Neubert, Reinhard H. H.
通讯作者：
Neubert, Reinhard H. H.
影响因子：
2.5
作者：
Iliopoulos, Fotis;Al Hossain, A. S. M. Monjur;Lane, Majella E.
通讯作者：
Lane, Majella E.
影响因子：
5.8
作者：
Mateus, R.;Abdalghafor, H.;Lane, M. E.
通讯作者：
Lane, M. E.