(T1430-05-25) Monitoring the Dissolution Behavior of Dissolving Microneedles by UV-Vis Imaging System

Purpose: As a new transdermal drug delivery system (TDDS), microneedle patches with tiny needles less than 1 mm in length that contain drugs are attracting attention. Microneedles allow drugs to cross the skin barrier painlessly. For this reason, microneedles are being researched for application not only to low-molecular compounds but also to vaccines.
In this study, we investigated a method to visually and quantitatively monitor the dissolution behavior of drugs from microneedles.

Methods: Preparation of microneedles: Microneedles were prepared by melting drug powder at 180°C under vacuum and molding it in a silicone mold. The silicon mold used had 100 needles within an area of 25 mm² (5 mm x 5 mm). Indomethacin and nifedipine were used as model compounds. HPMCAS, which has a melting point close to that of the model compounds, was used as the base of the microneedle patches. Monitoring of dissolution behavior: The microneedle patch was set in a flow-through cell type dissolution tester equipped with a UV-Vis imaging system.  Closed loop dissolution test was performed using a phosphate buffer solution of pH 7.2. During the dissolution test, LED light at wavelengths of 255 nm and 520 nm ware irradiated to monitor the dissolution behavior of the drugs from the microneedles.

Results: Uniform microneedles were obtained for both indomethacin and nifedipine. By imaging the inside of the flow-through cell with UV and Vis, we succeeded in observing the dissolution behavior of the drugs from the microneedles in real time. UV detected the behavior of the drug dissolution from the microneedles, while Vis detected undissolved microneedles and particles. Dissolution of indomethacin started immediately after the start of the test, and the final concentration of 1.6 µg/mL was reached approximately 40 minutes later. Dissolution of nifedipine microneedles was slow and continued to increase during the dissolution test, reaching 1.5 µg/mL after 12 hours.

Conclusion: When considering methods to evaluate drug dissolution behavior from microneedles, an important issue is how to create conditions like those on the skin. In this study, we conducted a flow-through cell type dissolution test, and attempted to evaluate the dissolution behavior from the needle part that punctured through the membrane. As a result, by combining UV and Vis imaging, we succeeded in visualizing the dissolution behavior of the microneedles. This method could be applied to both rapid and continuous dissolution types of microneedles. This system that combines flow-through cell and UV-Vis imaging is an effective way to simultaneously achieve visualization and quantitative evaluation for the dissolution behavior of drugs from microneedles.

References: 1. Sharvari M. Kshirsagar, Thomas Kipping, Ajay K. Banga,. Fabrication of Polymeric Microneedles using Novel Vacuum Compression Molding Technique for Transdermal Drug Delivery, Pharm. Res., (2022) 39(12), 3301-3315
2. Ziad Sartawi, Caroline Blackshields, Waleed Faisa, Dissolving microneedles: Applications and growing therapeutic potential, J. Control. Release (2022) 348,186–205


(Left) Overall image of microneedles molded into a 25mm2 square area.
(Right) Enlarged image of microneedles. The needles are aligned at a pitch of 500 µm.


Imaging the dissolution behavior of indomethacin microneedles. The needle position is surrounded by a blue frame.
(Left) Image acquired at a wavelength of 255 nm. The dissolution of indomethacin into the solution was visualized.
(Center) Image acquired at a wavelength of 520 nm. The shape of the needle in the solid state was visualized.
(Right) Picture inside the flow-through cell after the dissolution test. The microneedle patch was pressed against the artificial membrane so that only the tips of the needles that had broken through the membrane ware in contact with the test medium. The patch base was covered with the insoluble film.


Concentration monitoring results of compounds in the flow-through cell. (Left) Indomethacin, (Right) Nifedipine.