Double‐Layered Polyvinylpyrrolidone–Poly(methyl vinyl ether‐<i>alt</i>‐maleic acid)‐Based Microneedles to Deliver Meloxicam: An In Vitro, In Vivo, and Short‐Term Stability Evaluation Study
Carmine D’Amico, Flavia Fontana, Nesma El‐Sayed, Khalil Elbadri, Alexandra Correia, Antti Rahikkala, Jukka Saarinen, Mohammad‐Ali Shahbazi, Hélder A. Santos
Abstract
Abstract This study aims to explore the use of polymeric microneedles (MNs) for the transdermal delivery of drugs, a noninvasive and convenient method that avoids first‐pass metabolism and gastrointestinal complications. Specifically, a double‐layered MN formulation is developed using polyvinylpyrrolidone and cross‐linked poly(methyl vinyl ether‐ alt ‐maleic acid), comprising a dissolvable layer and a hydrogel‐forming layer. Meloxicam serves as the model drug, and no organic solvents are employed in the manufacturing process to reduce toxicity. Coherent anti‐Stokes Raman spectroscopy (CARS) is utilized to confirm that the manufacturing process does not alter the drug's physical properties. In vitro and ex vivo studies demonstrate that the double‐layered MN formulation exhibits faster drug release in the first few hours, followed by a slower release. This results in extended bioavailability in vivo compared to the commercial oral formulation of meloxicam. Preliminary results indicate that the MN formulation is also effective in pain relief and inflammation reduction. The short‐term stability of the MN formulation is also confirmed, including its mechanical properties, sustained skin permeability, drug physical properties and distribution within MNs using CARS microscopy. Overall, these results suggest that the double‐layered MN formulation holds significant potential for transdermal drug delivery, offering a safer and more effective alternative to traditional oral administration.