Microneedle assisted iontophoretic transdermal delivery of prochlorperazine edisylate

Abstract

This paper investigates the microneedle (MN) mediated in vitro transdermal iontophoretic delivery of prochlorperazine edisylate (PE) across dermatomed human skin. The Dermaroller™ induced microchannels were visualized using methylene blue staining and scanning electron microscopy. In vitro skin permeation studies were performed using vertical static Franz diffusion cells. Iontophoretic protocols involved application of direct current at a density of 0.4 mA/cm(2) using Ag as an anode and Ag/AgCl as a cathode. The effect of PE concentration (20, 50 and 100 mg/mL), number of passes of microneedles (0, 5, 10 and 20) on both iontophoretic and passive delivery of PE was studied. The Dermarollertm was found to successfully breach the skin barrier and a linear relationship (r(2) = 0.99) was observed between the number of passes of the Dermaroller™ and the number of microchannels created. Passive transdermal flux of PE (0.060 ± 0.003 µg/cm(2)/h) at 50 mg/mL donor PE concentration) was low and increased (4.15 ± 0.57 µg/cm(2)/h) with the application of direct current. Application of iontophoresis in conjunction with microneedle pre-treatment resulted in enhanced flux (4.90 ± 0.39 µg/cm(2)/h at 50 mg/mL donor PE concentration) of PE. The projected transdermal PE flux indicates that a 9 cm(2) patch could deliver PE in a sufficient amount to maintain therapeutic levels of the drug. In conclusion, microneedles when used in conjunction with iontophoresis significantly enhanced the transdermal delivery of PE and it may be feasible to develop an iontophoretic transdermal patch that could be integrated with MN.

Effect of Lipophilicity on Microneedle-Mediated Iontophoretic Transdermal Delivery Across Human Skin In Vitro

“…This is due to creation of micropores for the drug transport across the skin . However, the magnitude of increase is significantly smaller ( p < 0.001) as compared with ITP for respective drugs and this observation is consistent with earlier observations . The ER with MN increased with decrease in the lipophilicity of the drug (Table ).…”

“…A combination strategy that involves the usage of more than one enhancement technique can result in additive or synergistic delivery of drugs across the skin . ITP or MN acts independently of each other and each of them when used alone, are capable of enhancing skin permeation.…”

“…24 A combination strategy that involves the usage of more than one enhancement technique can result in additive or synergistic delivery of drugs across the skin. [25][26][27][28] ITP or MN acts independently of each other and each of them when used alone, are capable of enhancing skin permeation. ITP applied over MN pretreated skin has led to significant increase in the transdermal permeation of insulin and a fluorescein isothiocyanatelabeled bovine serum albumin across porcine skin as compared with either MN or ITP alone.…”

In Vivo Transdermal Delivery of Leuprolide Using Microneedles and Iontophoresis

“…This is the reason why the use of combination treatment resulted in higher delivery of proclorperazine edisylate and methotrexate as compared to either treatment used alone [24,36]. The driving force provided by electrorepulsion primarily depends upon the charge of the drug molecule and the number of molecules being pushed through the skin would increase with the increase in the pathways in the skin.…”

Effect of microporation on passive and iontophoretic delivery of diclofenac sodium

“…Indeed, the micro-damage to the skin produced by the microneedle rollers can possibly increase collagen production during the physiological repair process and thus improves the overall appearance of the skin. Lately, microneedle rollers have been evaluated to enhance transdermal drug delivery in vitro 13,14 and in vivo 15,16 . The main appeals of rollers are self-administration and low cost, combined with the flexibility to treat areas of various extensions, from small to very large.…”