AAPS PharmSciTech

, Volume 7, Issue 1, pp E163–E167 | Cite as

Effect of pH on sublingual absorption of oxycodone hydrochloride

  • Abeer M. Al-Ghananeem
  • Ahmad H. Malkawi
  • Peter A. Crooks


The purpose of this study was to develop a sublingual spray drug delivery formulation of oxycodone and evaluate the effect of formulation pH on sublingual absorption of oxycodone for acute pain management using rabbit as the animal model. Using a new, sensitive, and specific liquid chromatography/mass spectrometry (LC/MS) with electrospray ionization detector assay, the absorption bioavailability of sublingual oxycodone was determined in rabbits by comparing plasma concentration after sublingual spray delivery with equivalent intravenous dose. The effect of formulation pH on sublingual absorption of oxycodone was also tested on rabbits that had received oxycodone sublingually at a dose of 0.1 mg/0.1 mL (pH 4.0 and 9.0). Blood samples were collected at different time points, and plasma oxycodone concentrations were determined by LC/MS. Following administration of a 0.1 mg dose, the average Cmax values were found to be 64.9±12.1 and 95.2±10.1 ng/mL, for pH 4.0 and 9.0, respectively. The area under the curve (AUC) values were found to be 5807.0, and 8965.3 ng.min/mL for formulation pH 4.0 and 9.0, respectively. The mean sublingual bioavailability of oxycodone was 45.4%±20.1% and 70.1%±17.9%, for pH 4.0 and 9.0, respectively. the formulation pH had no significant influence on oxycodone bioavailability (P<.05). A sublingual spray dosage form of oxycodone hydrochloride would be a good alternative for fast onset pain management, especially in children.


oxycodone sublingual spray acute pain rabbit 


  1. 1.
    Lenz G, Evans S, Walters E, Hopfinger A. Opiates, Orlando, FL: Academic, 1987.Google Scholar
  2. 2.
    Kalso E. Oxycodone. J Pain Symptom Manage. 2005;29:S47-S56.CrossRefPubMedGoogle Scholar
  3. 3.
    Poyhia R, Vainio A, Kalso E. A review of oxycodone’s clinical pharmacokinetics and pharmacodynamics. J Pain Symptom Manage. 1993;8:63–67.CrossRefPubMedGoogle Scholar
  4. 4.
    Zhukovsky D, Walsh D, Doona M. The relative potency between high dose oral oxycodone and intravenous morphine: a case illustration. J Pain Symptom Manage. 1999;18:53–55.CrossRefPubMedGoogle Scholar
  5. 5.
    Poyhia R, Seppala T, Olkkola K, Kalso E. The pharmacokinetics and metabolism of oxycodone after intramuscular and oral administration to healthy subjects. Br J Clin Pharmacol. 1992; 33:617–621.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Takala A, Kaasalainen V, Seppala T, Kalso E, Olkkola K. Pharmacokinetic comparison of intravenous and intranasal administration of oxycodone. Acta Anaesthesiol Scand. 1997; 41:309–312.CrossRefPubMedGoogle Scholar
  7. 7.
    Kaufmann J, Yesiloglu S, Patermann B, Krombach J, Kiencke P, Kampe S. Controlled-release oxycodone is better tolerated than intravenous tranmadol/metamizol for postoperative analgesia after retinal-surgery. Curr Eye Res. 2004;28:271–275.CrossRefPubMedGoogle Scholar
  8. 8.
    Lauretti GR, Oliveira GM, Pereira NL. Comparison of sustained-release morphine with sustained-release oxycodone in advanced cancer patients. Br J Cancer. 2003;89:2027–2030.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Kaplan R, Parris WC, Citron ML, et al. Comparison of controlled-release and immediate-release oxycodone tablets in patients with cancer pain. J Clin Oncol. 1998;16:3230–3237.CrossRefPubMedGoogle Scholar
  10. 10.
    Maddocks I, Somogyi A, Abbott F, Hayball P, Parker D. Attenuation of morphine-induced delirium in palliative care by substitution with infusion of oxycodone. J Pain Symptom Manage. 1996;12:182–189.CrossRefPubMedGoogle Scholar
  11. 11.
    Leow K, Smith M, Watt J, Williams B, Cramond T. Comparative oxycodone pharmacokinetics in humans after intravenous, oral, and rectal administration. Ther Drug Monit. 1992;14:479–484.CrossRefPubMedGoogle Scholar
  12. 12.
    Kurosaki Y, Takatori T, Nishimura H, Nakayama T, Kimura T. Regional variation in oral mucosal drug absorption permeability and degree of keratinization in hamster oral cavity. Pharm Res. 1991; 8:1297–1301.CrossRefPubMedGoogle Scholar
  13. 13.
    Quintanar-Guerrero D, Villalobos-Garcia R, Alvarez-Colin E, Cornejo-Bravo JM. In vitro evaluation of the bioadhesive properties of hydrophobic polybasic gels containing N,N-dimethylaminoethyl methacrylate-co-methyl methacrylate. Biomaterials. 2001;22:957–961.CrossRefPubMedGoogle Scholar
  14. 14.
    Modi P, Mihic M, Lewin A. The evolving role of oral insulin in the treatment of diabetes using a novel RapidMist system. Diabetes Metab Res Rev. 2002;18:S38-S42.CrossRefPubMedGoogle Scholar
  15. 15.
    Katz M, Barr M. Sublingual absorption. III. A comparison of sublingual absorption from various tablet bases. J Am Pharm Assoc. 1955;44:476–480.CrossRefGoogle Scholar
  16. 16.
    Weinberg D, Inturrisi C, Reidenberg B, et al. Sublingual absorption of selected opioids analgesics. Clin Pharmacol Ther. 1988;44:335–342.CrossRefPubMedGoogle Scholar
  17. 17.
    Schanker LS. Passage of drugs across body membranes. Pharmacol Rev. 1962;14:501–530.PubMedGoogle Scholar
  18. 18.
    Zhang H, Zhang J, Streisand J. Oral mucosal drug delivery: clinical pharmacokinetics and therapeutic applications. Clin Pharmacokinet. 2002;41:661–680.CrossRefPubMedGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2006

Authors and Affiliations

  • Abeer M. Al-Ghananeem
    • 1
  • Ahmad H. Malkawi
    • 1
  • Peter A. Crooks
    • 1
  1. 1.Department of Pharmaceutical Sciences, College of PharmacyUniversity of KentuckyLexington

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