title: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine Hannover, Foundation, Buenteweg 17, Hannover 30559, Germany. xjessica.stahl@tiho-hannover.de
authors.forename: Jessica
authors.initials: J
authors.lastname: Stahl
authors.forename: Mareike
authors.initials: M
authors.lastname: Wohlert
authors.forename: Manfred
authors.initials: M
authors.lastname: Kietzmann
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage / Q000737:chemistry; D000279:Administration, Cutaneous; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000737:chemistry; D002417:Cattle; D004008:Diclofenac / Q000008:administration & dosage / Q000737:chemistry; D005260:Female; D057927:Hydrophobic and Hydrophilic Interactions; D007052:Ibuprofen / Q000008:administration & dosage / Q000737:chemistry; D066298:In Vitro Techniques; D007660:Ketoprofen / Q000008:administration & dosage / Q000737:chemistry; D009339:Needles; D012869:Skin Absorption; D044366:Transition Temperature
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004008:Diclofenac; D000082:Acetaminophen; D007660:Ketoprofen; D007052:Ibuprofen