Instantaneous topical drug quantification using a 3D printed microfluidic device and coherent Raman imaging

• Published in: OpenNano Vol. 12; p. 100151
• Main Authors: Kuzma, Benjamin A., Tu, Dandan, Goss, Avery, Iliopoulos, Fotis, Slade, Julian Byrne, Wiatrowski, Anna, Feizpour, Amin, Evans, Conor L.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01-07-2023; Elsevier
• Subjects: 3D printing; Active pharmaceutical ingredient; Cutaneous pharmacokinetics; Stimulated Raman scattering; Topical drug delivery; Cutaneous pharmacokinetics; Topical drug delivery; Active pharmaceutical ingredient; Stimulated Raman scattering; 3D printing
• ISSN: 2352-9520; 2352-9520
• DOI: 10.1016/j.onano.2023.100151

•Developed a 3D-printed applicator to monitor active pharmaceutical ingredients immediately after topical application.•S4RS and the 3D printed applicator captures differences in exposure in frozen skin.•3D printed applicator requires low formulation volume, is low-cost, and achieves low sample drift.•Propylene glycol provides more rapid permeation of RUX compared to DGME.
Cutaneous drug concentration quantification after topical application remains an active, yet challenging research area for topical drug development. Macroscale approaches quantify cutaneous pharmacokinetics 30  min to hours after application and miss rapid temporal and spatial dynamics that are vital to comprehend drug disposition. We have developed a 3D-printed applicator coupled with an inverted microscope and a rapidly-tunable fiber optic laser to quantify active pharmaceutical ingredients via sparse spectral sampling stimulated Raman scattering. The 3D-printed applicator is cost-effective (< $0.70/applicator) and utilizes a small formulation volume (20 µL). Ruxolitinib was formulated in two known permeation enhancers (propylene glycol and diethylene glycol monoethyl ether) that are known to display different permeation profiles to validate device capabilities. Results indicated that the applicator enabled relative-concentration monitoring immediately following drug product application. This approach has significant potential for investigating novel excipients, active pharmaceutical ingredients, and formulations to understand the permeation and biodistribution of these compounds.
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