Abstract
Background:
Phase I, randomized, controlled patch studies were conducted to evaluate skin sensitization
and irritation potential of a new gel formulation containing 1% diclofenac and 3%
menthol as a fixed-combination product.
Methods:
In study A, healthy volunteers were exposed to 4 test patches containing 1% diclofenac+3%
menthol, diclofenac, menthol, or placebo gels during an induction (nine 48 to 72-h
applications) and challenge phase (one 48-h application). Some subjects were re-challenged
to evaluate suspected sensitization. Study B participants underwent 21 consecutive
24-h patch applications of the 4 treatments from study A, 0.2% sodium lauryl sulfate
(positive control), 0.9% saline, and a marketed gel (1% diclofenac, Voltaren). Application
sites were visually scored by blinded observers for skin sensitization/irritation.
Results:
In study A, 77% of participants showed minimal erythema and signs of glazing and peeling
with 1% diclofenac+3% menthol by the end of the induction phase, which diminished
during the challenge phase. Similar patterns were seen with menthol gel. Only 1 subject
exhibited possible sensitization to 1% diclofenac+3% menthol. In study B, mean cumulative
irritation score with 1% diclofenac+3% menthol was significantly higher (P <0.0001) vs. reference treatments; however, the positive control failed to produce
the expected level of irritation. No treatment-related adverse events were reported.
Conclusions:
The sensitization and irritation potential of 1% diclofenac+3% menthol was greater
than with the reference treatments. Comparison with positive control was not possible
because it did not produce irritation under semiocclusive patch conditions.
Key words skin pharmacology - analgesic drugs - drug research
