title: Iontophoretic and microneedle mediated transdermal delivery of glycopyrrolate.
abstract: OBJECTIVE
  The objective of this study was to investigate the use of iontophoresis, soluble microneedles and their combination for the transdermal delivery of glycopyrrolate.
  
  
  METHODS
  In vitro permeation was tested using full thickness porcine ear skin mounted onto Franz diffusion cells. Iontophoresis (0.5 mA/cm2) was done for 4 h using Ag/AgCl electrodes. For microneedles, three line array (27 needles/line) of maltose microneedles were used to microporate the skin prior to mounting. Pore uniformity was determined by taking fluorescent images of distribution of calcein into pores and processing the images using an image analysis tool, which measured the fluorescent intensity in and around each pore to provide a pore permeability index (PPI). The donor chamber contained 500 µL of a 1 mg/mL solution of glycopyrrolate, and the receptor chamber contained 5 mL of 50 mM NaCl in deionized water. Samples were collected at predetermined time points over a period of 24 h and analyzed by HPLC. Skin irritation testing was performed with a 3D cell culture kit of human skin. MTT assay determined cell viability; viability less than 50% was considered irritant.
  
  
  RESULTS
  A control experiment which investigated passive permeation of glycopyrrolate delivered an average cumulative amount of 24.92 ± 1.77 µg/cm2 at 24 h, while microneedle pretreatment increased permeability to 46.54 ± 6.9 µg/cm2. Both iontophoresis (158.53 ± 17.50 µg/cm2) and a combination of iontophoresis and microneedles (182.43 ± 20.06 µg/ cm2) significantly increased delivery compared to passive and microneedles alone. Glycopyrrolate solution was found to be nonirritant with cell viability of 70.4% ± 5.03%.
  
  
  CONCLUSIONS
  Iontophoresis and a combination of iontophoresis with microneedle pretreatment can be effectively used to enhance the transdermal delivery of glycopyrrolate. Glycopyrrolate was found to be non-irritant to skin.
authors.affiliation: Department of Pharmaceutical Sciences, Mercer University, 3001 Mercer University Drive, Atlanta, GA 30341, USA. Meera.Suresh.Gujjar@live.mercer.edu.
authors.forename: Meera
authors.initials: M
authors.lastname: Gujjar
authors.affiliation: Department of Pharmaceutical Sciences, Mercer University, 3001 Mercer University Drive, Atlanta, GA 30341, USA. Banga_ak@mercer.edu.
authors.forename: Ajay K
authors.initials: AK
authors.lastname: Banga