Topical application of a novel oxycodone gel formulation (tocopheryl phosphate mixture, TPM) in a rat model of peripheral inflammatory pain produces localized pain relief without significant systemic exposure

Smith, Maree T., Wyse, Bruce D., Edwards, Stephen R., El-Taminy, Mahmoud, Gaetano, Giacinto and Gavin, Paul (2015) Topical application of a novel oxycodone gel formulation (tocopheryl phosphate mixture, TPM) in a rat model of peripheral inflammatory pain produces localized pain relief without significant systemic exposure. Journaal of Pharmaceutical Sciences, 104 7: 2388-2396. doi:10.1002/jps.24502


Author Smith, Maree T.
Wyse, Bruce D.
Edwards, Stephen R.
El-Taminy, Mahmoud
Gaetano, Giacinto
Gavin, Paul
Title Topical application of a novel oxycodone gel formulation (tocopheryl phosphate mixture, TPM) in a rat model of peripheral inflammatory pain produces localized pain relief without significant systemic exposure
Journal name Journaal of Pharmaceutical Sciences   Check publisher's open access policy
ISSN 1520-6017
0022-3549
Publication date 2015-07-01
Year available 2015
Sub-type Article (original research)
DOI 10.1002/jps.24502
Open Access Status Not yet assessed
Volume 104
Issue 7
Start page 2388
End page 2396
Total pages 9
Place of publication Hoboken, NJ United States
Publisher John Wiley & Sons
Language eng
Abstract 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.
Keyword Transdermal drug delivery
Permeation enhancers
Absoption
Gels
Formulation
Tocopheryl phosphate mixture
Oxycodone
Analgesia
Antihyperalgesia
Inflammatory pain
Topical gel
Strong opioid analgesic
Rat model
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Pharmacy Publications
 
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Created: Sat, 23 May 2015, 19:45:37 EST by Professor Maree Smith on behalf of School of Pharmacy