Microneedle pretreatment enhances the percutaneous permeation of hydrophilic compounds with high melting points

Abstract

BACKGROUND: Two commercially available microneedle rollers with a needle length of 200 μm and 300 μm were selected to examine the influence of microneedle pretreatment on the percutaneous permeation of four non-steroidal anti-inflammatory drugs (diclofenac, ibuprofen, ketoprofen, paracetamol) with different physicochemical drug characteristics in Franz-type diffusion cells. Samples of the receptor fluids were taken at predefined times over 6 hours and were analysed by UV-VIS high-performance liquid-chromatography. Histological examinations after methylene blue application were additionally performed to gather information about barrier disruption. RESULTS: Despite no visible pores in the stratum corneum, the microneedle pretreatment resulted in a twofold (200 μm) and threefold higher (300 μm) flux through the pretreated skin samples compared to untreated skin samples for ibuprofen and ketoprofen (LogK(ow) > 3, melting point < 100°C). The flux of the hydrophilic compounds diclofenac and paracetamol (logK(ow) < 1, melting point > 100°C) increased their amount by four (200 μm) to eight (300 μm), respectively. CONCLUSION: Commercially available microneedle rollers with 200-300 μm long needles enhance the drug delivery of topically applied non-steroidal anti-inflammatory drugs and represent a valuable tool for percutaneous permeation enhancement particularly for substances with poor permeability due to a hydrophilic nature and high melting points.