Stimulated Raman scattering (SRS) microscopy enables label-free and quantitative imaging of active pharmaceutical ingredients within the skin, with superior chemical specificity and spatial and temporal resolution. Here, we present a method to study topical formulations on ex vivo human skin using two modalities, SRS and near-infrared light (NIR) transmission. NIR transmission is used to compensate for the SRS signal variance caused by differences in skin thickness and formulation properties. Optical co-registration of the two modalities enables recording the variance in each pixel. The developed method helps to evaluate the cutaneous pharmacokinetics of tretinoin from tretinoin-containing solution and cream formulations.
The bioequivalence of pharmaceutical formulations is typically demonstrated by assessing the pharmacokinetics (PK) of a generic product relative to a reference listed drug (RLD) product. However, for topical products applied to the skin, it has been historically challenging to quantify the drug concentration at the target site of action, and therefore the applicability of the PK-based approach has been limited. Here, we present a novel approach based on stimulated Raman scattering imaging and data processing via deep learning for image feature extraction and automated analysis of cutaneous PK parameters, which also enables the imaging of drug distribution in real time.
Being able to visualize and quantify where the drug and/or excipient resides within a multiphasic formulation, how the drug diffuses and is released from the dosage form, the delivery and disposition of the drug and performance of the dosage form can be a powerful tool towards development of dermal drug products. The presentation will focus on how imaging techniques can be used for evaluation of the dosage form and the availability of the drug/excipients in the different layers of the skin to facilitate drug development.
(Abstract was accepted and redacted last year due to travel restrictions)
Being able to visualize and quantify where an active ingredient and/or excipient resides within a multiphasic formulation (e.g., a semisolid emulsion), how the drug diffuses and is released from the dosage form, and the delivery and disposition of the drug at the intended site of action can be a powerful tool the development of locally acting drug products such as a dermatological cream. The presentation will focus on how techniques for the evaluation of cutaneous pharmacokinetics have evolved over the years, and how noninvasive imaging-based techniques are being utilized to mechanistically understand drug availability and drug disposition following topical application.
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