While there is substantial evidence proving the success of transdermal
drug delivery, there have been few accomplishments in the area of dep
th-resolved prediction of drug concentration during diffusion through
a matrix. Such a method for noninvasive quantification of a diffusing
species could assist in the development of new drugs, dosage forms, an
d penetration enhancers. Near-infrared depth-resolved measurements wer
e accomplished by strategically controlling the amount of reflected li
ght reaching the detectors using a combination of diaphragms with diff
erent-diameter apertures. Near-IR spectra were collected from a set of
cellulose and Silastic(R) membranes to prove the possibility of depth
-resolved near-IR measurements. Principal component regression was use
d to estimate the depth resolution of this method, yielding an average
resolution of 31 mu m. Further, to demonstrate depth-resolved near-IR
spectroscopy in a practical in vitro system, we determined concentrat
ions of salicylic acid (SA) in a hydrogel matrix during diffusion expe
riments carried out for up to three hours. An artificial-neural-networ
k-based calibration model was developed which predicted SA concentrati
ons accurately (R(2) = 0.993, SEP = 123 mu g/mL).