Vehicle Composition Influence on the Microneedle-Enhanced Transdermal Flux of Naltrexone Hydrochloride

Purpose Transdermal delivery of drugs is often limited by formidable barrier properties of stratum corneum (SC). Microneedles (MN) enable creation of transient microchannels in the SC and bypass this barrier. Many reports have focused on the great effectiveness of MN in improving percutaneous flux values of a variety of drugs over a large molecular size spectrum. The objective of the present study is to evaluate the influence of formulation on MN-enhanced transdermal transport of naltrexone hydrochloride (NTX HCl). Methods A series of in vitro experiments employing binary mixtures of propylene glycol (PG) and water as vehicle were used with either MN-treated or untreated skin. A simple model taking into account two parallel flux values through intact skin and microchannels was used to analyze data. Results Transdermal permeation of NTX HCl from different donor solutions indicated that PG-rich formulations greatly limited MN-enhanced transport but had a much smaller effect on transport through intact skin. Conclusions Diffusion through the microchannel pathway seems to be donor viscosity-related and follows the relationship predicted by the Stokes-Einstein equation as shown by linear dependence of flux on diffusivity of NTX in donor solutions.