Transport Pharmaceuticals, Inc.

Efficient iontophoretic transdermal delivery of hydrophilic drug molecules requires selection of appropriate aqueous formulation. In this study, oil/water cream and gel formulations were investigated for iontophoretic transdermal delivery of acyclovir (ACV), a model hydrophilic small-drug molecule, across hairless rat skin on Franz diffusion cells.

Iontophoresis (0.2 mA/cm2) enhanced ACV delivery from both 5% cream (pH 6.8) and 4% gel (pH II) formulations. However, sixfold higher drug levels were delivered across the skin using gel formulation (12.25 +/- 4.04 microg/cm2) as compared with cream formulation (2.03 +/- 0.05 microg/cm2). Significantly higher drug levels were delivered when iontophoresis was performed at higher current density (0.32 mA/cm2; p < 0.05). Influence of formulation co-solvents (glycerin and propylene glycol) on drug delivery was also investigated in vitro using Franz cells and in vivo in hairless rats using microdialysis.

Iontophoretic transdermal delivery of ACV was feasible and dependent on the selection of formulation components and delivery parameters.

Ion exchange chelation chromatography is an effective means to extract metals from coordination complexes and biological samples; however there is a lack of data to verify the nature of metal complexes that can be successfully analysed using such a procedure. The aim of this study was to assess the capability of pyridine 2,6‐dicarboxylic acid (PDCA) to extract and quantify Ga(III) from a range of environments using standard liquid chromatography apparatus. The PDCA chelation method generated a single Ga(III) peak with a retention time of 2.55 ± 0.02 min, a precision of <2% and a limit of detection of 110 μM. Ga(III) hydroxide complexes (highest stability constant 15.66) were used to successfully cross‐validate the chelation method with inductively coupled plasma mass spectrometry. The PDCA assay extracted 96.9 ± 1.2% of the spiked Ga(III) from porcine mucus and 100.7 ± 2.7% from a citrate complex (stability constant 10.02), but only ca 50% from an EDTA complex (stability constant 22.01). These data suggest that PDCA chelation can be considered a suitable alternative to inductively coupled plasma mass spectrometry for Ga(III) quantification from all but the most strongly bound coordinated complexes i.e. a stability constant of <15. Copyright © 2010 John Wiley & Sons, Ltd.

An iontophoretic treatment system for onychomycosis, using drug applicators targeting either toe nail only or nail and surrounding tissue, is analyzed. Phase 1 clinical data shows levels of drug delivery that differ unexpectedly from relative dosing level to multiple tissue types. Current monitoring and analysis techniques, coupled with assays of drug delivery into excised nail and cadaver toe, were used to evaluate drug delivery vs. current flow. The results indicate good correlation with piecewise linear models of current flow and extracted drug in the nail-only application. For the nail and surrounding tissue application, assayed drug levels indicate that on average, drug load per unit dose (mA-min) is more efficient into nail than into surrounding tissue (2.38:1 ug/mA-min nail vs. surrounding tissue, n=6, p=0.009).