For the clinical evaluation, 160 human subjects were given a 50 μg LT dose in either a wet or dry patch. Each subject was
immunized twice, at Day 0 and Day 21. Blood serum samples were collected from each subject on Days 7, 14, 21, 28, 35, and
42, for determination of LT IgG and LT IgA titers.
Factorial analysis using LT IgG titers and fold rise (ratio to baseline titers) indicated that the dry patch produced statistically
significantly higher titers and fold ratios of LT IgG and IgA than did the wet patch at all timepoints from Day 14 onward
(Figure 5). This study demonstrated that the dry LT patch is equal to or better than the wet patch at the same dosage in terms
of vaccine delivery. We surmise that the dry patch formulation is readily solubilized by transepidermal water loss, resulting
in a greater LT concentration gradient at the surface of the skin compared to the wet patch. This higher concentration gradient
provides the thermodynamic driving force to deliver more adjuvant into the skin.
Figure 5. Human subjects received either a "wet" or "dry" patch containing 50μg LT on Day 0 and Day 21. LT IgG titers were
measured on Days 7, 14, 21, 28, 35, and 42, and compared to baseline titers. The mean fold rise in LT IgG is indicated by
the red and blue lines for the "dry" and "wet" patch, respectively.
Dry Formulation Optimization and Patch Design
Since the clinical trial involving the dry versus wet patches, our laboratory has continued to optimize the dry formulation
matrix and to develop the final patch format for transcutaneous delivery. To this end, our current dry patch contains a proprietary
stabilizing matrix that is compatible with biological molecules and vaccine antigens. The dry patch is prepared by dosing
a small volume (20–40 μL) of the drug substance blend onto an absorbent matrix with a surface area ranging from 1–3 cm2 , followed by drying under moderate conditions in a convection oven. The LT-dosed matrix is assembled with an occlusive backing,
release liner and adhesive overlay, and sealed in a nitrogen-purged foil pouch for storage at 2–8 °C (Figure 6). When applied
to the skin, the dry patch formulation is readily hydrated by skin moisture (transepidermal water loss) and effectively releases
the antigens, adjuvant, or both into the skin. The patch is removed after six hours of wear.
Figure 6. Schematic representation of the IS patch showing patch components and application to the arm.
LT Dry Patch Thermostability
The drug substance(s) and excipients are extracted from the patch and this extract is then used in the various analytical
assays. Only key stability-indicating assays will be discussed in this paper.