This study was designed to assess the
analgesic efficacy and systemic exposure of
oxycodone administered topically in a novel
tocopheryl phosphate mixture (TPM) gel formulation, to the inflamed hindpaws in a rat model of inflammatory
pain. Unilateral hindpaw
inflammation was induced in male Sprague-Dawley rats by intraplantar (i.pl.) injection of Freund's complete adjuvant (FCA).
Mechanical hyperalgesia and hindpaw
inflammation were assessed by measuring paw pressure thresholds and hindpaw volume, respectively, just prior to i.pl. FCA and again 5-6 days later. The
analgesic effects of
oxycodone administered topically (1 mg in TPM gel) or by i.pl. injection (50 μg), were assessed. Systemic
oxycodone exposure was assessed over an 8-h postdosing interval following topical application. Skin permeation of
oxycodone from the gel formulation was assessed in vitro using Franz diffusion cells.
Oxycodone administered topically or by i.pl. injection produced significant (p < 0.05)
analgesia in the inflamed hindpaws. Systemic
oxycodone exposure was insignificant after topical dosing. The in vitro cumulative skin permeation of
oxycodone was linearly related to the amount applied. Topical TPM/
oxycodone gel formulations have the potential to alleviate moderate to severe inflammatory
pain conditions with minimal systemic exposure, thereby avoiding central nervous system (CNS)-mediated adverse effects associated with
oral administration of
opioid analgesics.