Topical Application of a Novel Oxycodone Gel Formulation (Tocopheryl Phosphate Mixture) in a Rat Model of Peripheral Inflammatory Pain Produces Localized Pain Relief Without Significant Systemic Exposure

Journal of Pharmaceutical Sciences

Volumn 104, Issue 7, 2015, Pages 2388-2396

  Smith, Maree T ^a   Wyse, Bruce D ^a   Edwards, Stephen R ^a   El Tamimy, Mahmoud ^b   Gaetano, Giacinto ^b   Gavin, Paul ^b  

^a UNIVERSITY OF QUEENSLAND   (Australia)

^b Phosphagenics Limited Australia   (Australia)

Author keywords

Absorption; Analgesia; Antihyperalgesia; Formulation; Gels; Inflammatory pain; Oxycodone; Permeation enhancers; Tocopheryl phosphate mixture; Transdermal drug delivery

Indexed keywords

DRUG CARRIER; OXYCODONE; TOCOPHERYL PHOSPHATE MIXTURE; UNCLASSIFIED DRUG; ALPHA TOCOPHEROL; ALPHA-TOCOPHEROL PHOSPHATE; ANALGESIC AGENT; GEL; NARCOTIC ANALGESIC AGENT; NONSTEROID ANTIINFLAMMATORY AGENT;

ANALGESIA; ANALGESIC ACTIVITY; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BLOOD LEVEL; CONTROLLED STUDY; DRUG DOSAGE FORM COMPARISON; DRUG EFFICACY; DRUG PENETRATION; GEL; IN VITRO STUDY; INFLAMMATORY PAIN; INTRAPLANTAR DRUG ADMINISTRATION; MALE; NONHUMAN; RAT; RAT MODEL; SKIN PERMEABILITY; SYSTEMIC THERAPY; TOPICAL TREATMENT; TREATMENT OUTCOME; ADMINISTRATION AND DOSAGE; ANALOGS AND DERIVATIVES; ANIMAL; INFLAMMATION; MEDICINAL CHEMISTRY; PAIN; PAIN MEASUREMENT; PROCEDURES; SPRAGUE DAWLEY RAT;

ALPHA-TOCOPHEROL; ANALGESICS; ANALGESICS, OPIOID; ANIMALS; ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL; CHEMISTRY, PHARMACEUTICAL; GELS; INFLAMMATION; MALE; OXYCODONE; PAIN; PAIN MANAGEMENT; PAIN MEASUREMENT; RATS; RATS, SPRAGUE-DAWLEY;

EID: 84934886475     PISSN: 00223549     EISSN: 15206017     Source Type: Journal    
DOI: 10.1002/jps.24502     Document Type: Article

References (29)

1. Schaible HG, Ebersberger A, Natura G,. 2011. Update on peripheral mechanisms of pain: Beyond prostaglandins and cytokines. Arthritis Res Ther 13 (2): 210-218.
2. Schaible HG, Richter F,. 2004. Pathophysiology of pain. Langenbecks Arch Surg 389 (4): 237-243.
3. Breedveld FC., 2004. Osteoarthritis-The impact of a serious disease. Rheumatology 43 (Suppl 1): i4-i8.
4. Crofford LJ., 2013. Use of NSAIDS in treating patients with arthritis. Arthritis Res Ther 15 (Suppl 3): S2.
5. Riley J, Eisenberg E, Muller-Schwefe G, Drewes AM, Arendt-Nielsen L,. 2008. Oxycodone: A review of its use in the management of pain. Curr Med Res Opin 24 (1): 175-192.
6. Taylor R, Raffa R, Pergolizzi JV,. 2012. Controlled release formulation of oxycodone in patients with moderate to severe chronic osteoarthritis: A critical review of the literature. J Pain Res 5: 77-87.
7. Betses M, Brennan T,. 2013. Abusive prescribing of controlled substances-A pharmacy view. N Engl J Med 369 (11): 989-991.
8. Stein C, Lang LJ,. 2009. Peripheral mechanisms of opioid analgesia. Curr Opin Pharmacol 9 (1): 3-8.
9. Stein C, Shafer M, Machelska H,. 2003. Attacking pain at its source: New perspectives on opioids. Nat Med 9 (8): 1003-1008.
10. Hadley G, Derry S, Moore RA, Wiffen PJ,. 2013. Transdermal fentanyl for cancer pain. Cochrane Database Syst Rev 10: CD010270.
11. Corli O, Roberto A,. 2014. Pharmacological and clinical differences among transmucosal fentanyl formulations for the treatment of breakthrough cancer pain. Minerva Anestesiol 80 (10): 1123-1134.
12. Gavin P, Griffey A, Gianello R, Kennedy N, Keah HH,. 2008. Transdermal delivery of various molecules in vivo using alpha-tocopheryl phosphate. Drug Deliv Technol 8 (9): 34-41.
13. Olsen Y, Sharfstein JM,. 2014. Chronic pain, addiction, and Zohydro. N Engl J Med 370 (22): 2061-2063.
14. Gavin PD, El-Tamimy M, Cottrell JJ, Gaetano G, Kennedy NJ,. 2011. Carrier composition. Patent WO2011075775 A1.
15. Edwards SR, Smith MT,. 2007. Low level quantitation of oxycodone and its oxidative metabolites, noroxycodone, and oxymorphone in rat plasma by high performance liquid chromatography-Electrospray ionization-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 848 (2): 264-270.
16. Nielsen CK, Ross FB, Lotfipour S, Saini KS, Edwards SR, Smith MT,. 2007. Oxycodone and morphine have distinctly different pharmacological profiles: Radioligand binding and behavioural studies in two rat models of neuropathic pain. Pain 132 (3): 289-300.
17. Stein C, Zollner C,. 2009. Opioids and sensory nerves. Handb Exp Pharmacol 194: 495-518.
18. Jagla C, Martus P, Stein C,. 2014. Peripheral opioid receptor blockade increases postoperative morphine demands-A randomized, double-blind, placebo-controlled trial. Pain 155 (10): 2056-2062.
19. Hassan AHS, Ableitner A, Stein C, Herz A,. 1993. Inflammation of the rat paw enhances axonal transport of opioid receptors in the sciatic nerve and increases their density in the inflamed tissue. Neuroscience 55 (1): 185-195.
20. Stein C, Millan MJ, Shippenberg TS, Peter K, Herz A,. 1989. Peripheral opioid receptors mediating antinociception in inflammation. Evidence for involvement of mu, delta and kappa receptors. J Pharmacol Exp Ther 248 (3): 1269-1275.
21. Binder W, Machelska H, Mousa S, Schmitt T, Riviere PJM, Junien JL, Stein C, Schafer M,. 2001. Analgesic and anti-inflammatory effects of two novel κ-opioid peptides. Anesthesiology 94 (6): 1034-1044.
22. Lalovic B, Kharasch E, Hoffer C, Risler L, Liu-Chen LY, Shen DD,. 2006. Pharmacokinetics and pharmacodynamics of oral oxycodone in healthy human subjects: Role of circulating active metabolites. Clin Pharmacol Ther 79 (5): 461-479.
23. Kuo A, Wyse BD, Meutermans W, Smith MT,. 2015. In vivo profiling of seven common opioids for antinociception, constipation and respiratory depression: No two opioids have the same profile. Br J Pharmacol 172 (2): 532-548.
24. Cabot PJ, Carter L, Gaiddon C, Zhang Q, Schafer M, Loeffler JP, Stein C,. 1997. Immune cell-derived β-endorphin: Production, release, and control of inflammatory pain in rats. J Clin Invest 100 (1): 142-148.
25. Machelska H, Cabot PJ, Mousa SA, Zhang Q, Stein C,. 1998. Pain control in inflammation governed by selectins. Nat Med 4 (12): 1425-1428.
26. Rittner HL, Brack A, Machelska H, Mousa SA, Bauer M, Schafer M, Stein C,. 2001. Opioid peptide-expressing leukocytes: Identification, recruitment, and simultaneously increasing inhibition of inflammatory pain. Anesthesiology 95 (2): 500-508.
27. Sharp BM., 2006. Multiple opioid receptors on immune cells modulate intracellular signalling. Brain Behav Immun 20 (1): 9-14.
28. Michaelis M, Leopold CS,. 2014. Mixture design approach for early stage formulation development of a transdermal delivery system. Drug Dev Ind Pharm Oct 13: 1-9. [Epub ahead of print]
29. Trivedi JS, Krill SL, Fort JJ,. 1995. Vitamin E as a human skin penetration enhancer. Eur J Pharm Res 3: 241-243.