Piroxicam/Cyclodextrin: 35 years on the market

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On the occasion of the 25th anniversiary of cyclodextrin/piroxicam complex’ launching on the market a review of C. Scarpignato in 2013 gave an overview on this nonsteroidal anti-inflammatory drug (NSAID) covering the details on the development, pharmacokinetic properties and efficacy of the cyclodextrin formulation [1].
Complexation of piroxicam, with βCD potentially leads to a more rapid onset of action after oral dministration and improved GI tolerability because of minimization of the drug gastric effects. In the early studies the 2:1 stoichiometry has been proved by X-ray diffractometry and molecular dynamics calculations (Fig. 1) [2]. Based on these results the molar ratio of 2.5:1 has been applied in the commercial products produced and marketed by Chiesi [3]. To improve the patients compliance and reduce the GI irritation, effervescent tablets and sachet formulations were worked out and marketed under various trade names such as Brexin®, Cycladol®, and Flamexin®. As it became generic further trade names, such as Brexidol, Brexicam, Briax, Cyclodex, Cicladol , Dexpir, Flamexin, Medicam and Pyrodex can be found [4]. Suppository and pediatric formulations (Brexin, Flogene, respectively) are malso available. Recently further formulations of the complex were developed such as orally disintegrating tablet [5], fast dissolving electrospun nanofiber [6] and a nanosponge formuklation [7].
The analgesic and anti-inflammatory efficiency of the complex was at least as high as that of the pure drug in rats [8]. Pronounced and marked gastric ulceration with complete loss of the mucosa, extensive deposition of fibrin and dense neutrophilic infiltrate were observed in rats treated with Piroxicam alone while no damaged tissues were found in rats treated with the complex [9].
Randomized crossover single- and multiple-dose studies of Piroxicam/βCD in healthy volunteers have confirmed the expected more rapid absorption of this formulation, compared with uncomplexed piroxicam without significantly changing the other pharmacokinetic parameters [10].
The fast onset and enhanced duration of action were proved in patients with dysmenorrhea [11], postoperative [12] and dental pain [13], headache [14], back pain [15], degenerative or inflammatory knee diseases [16], etc. The efficiency in pain relief was usually similar to that of the free Piroxicam but better tolerated in the upper GI tract.
A detailed analysis of nearly 100 published and unpublished studies of Piroxicam/βCD documenting the incidence of minor and major GI adverse events in a total of 29,190 patients showed that the incidence of minor GI events was lower for the complex (0.07-1.37%) than for Piroxicam alone (0-6.4%) or placebo (0.11-3.21%) or the other reference agents (0.1- 3.45%), while hardly any major events were recorded during chronic treatment with the complex [1].
Ten years ago Scarpignato concluded that “after 25 years of use in Europe and South America, also Piroxicam/βCD – like piroxicam – has stood the test of time and, on the grounds of its efficacy and safety, should be considered as a useful addition to our therapeutic armamentarium” [1].


  1. Scarpignato, C.: Piroxicam-β-Cyclodextrin: A GI Safer Piroxicam. Curr. Med. Chem. 2013; 20(19):
    2415–2437. Published online 2013 June. doi: 10.2174/09298673113209990115
  2. Chiesi-Villa, A., Rizzoli, C., Amari, G., Delcanale, M., Redenti, E., Ventura, P.: The crystal structure of
    the inclusion complex of the sodium salt of piroxicam with β-cyclodextrin. Supramol. Chem. 1998; 10:111–119.
  3. Chiesi, P., Servadio, V.: Antiinflammatory drugs produced by complexation of piroxicam with cyclodextrins. Belg. Pat. 900836, 1985
  4. Puskás, I., Szente, L., Szőcs, L., Fenyvesi, É. “Recent List of Cyclodextrin-Containing Drug Products”, Periodica Polytechnica Chemical Engineering, 2023, 67, 11-17.
  5. Patel, M. A.; Shah, J. A.; Patel, B. A.; Patel, K. N.; Patel, P. A.: Formulation, optimization and
    evaluation of orally disintegrating tablet of non-steroidal anti-inflammatory drug. Int. J. Pharm. Res. Scholars 2012; 1(2):190-205
  6. Topuz, F. Rapid Sublingual Delivery of Piroxicam from Electrospun Cyclodextrin Inclusion Complex Nanofibers. ACS Omega 2022; 7, 39, 35083–35091.
  7. Raffaini, G.; Ganazzoli, F. Understanding Surface Interaction and Inclusion Complexes between Piroxicam and Native or Crosslinked β-Cyclodextrins: The Role of Drug Concentration. Molecules 2020, 25, 2848.
  8. Amado, C.A. Bersani, Taniguchi, S.F., Sudo, L.S., Kimura, E., Oga, S.: Effect of piroxicam βcyclodextrin complex on experimental inflammation. Gen. Pharmacol. 1995; 26:809–813.
  9. Alsarra, I.A., Ahmed, M.O., Alanazi, F.K., Eltahir, K.E., Alsheikh, A.M., Neau, S.H.: Influence of
    cyclodextrin complexation with NSAIDs on NSAID/cold stress-induced gastric ulceration in rats. Int. J. Med. Sci. 2010; 7:232–239
  10. Acerbi, D., Labecq, E., Jr, Rondelli, I., Stockis, A., Ventura, P.: Rapid oral absorption profile of
    piroxicam from its β-cyclodextrin complex. Drug Invest. 1990; 2(Suppl 4):50–55.
  11. Costa, S.: Prostaglandin synthetase inhibitor piroxicam beta-cyclodextrin in the treatment of primary
    dysmenorrhea. Curr. Ther. Res. 1987; 42:156–164.
  12. Simone, C., Oliani, C.: Beta-cyclodextrin-piroxicam: efficacy and tolerability in the treatment of pain
    after bone and joint surgery. Curr. Ther. Res. 1990; 47:541–547
  13. Dolci, G., Ripari, M., Pacifici, L., Umile, A.: Evaluation of piroxicam-beta-cyclodextrin, piroxicam,
    paracetamol and placebo in post-operative oral surgery pain. Int. J. Clin. Pharmacol. Res. 1994; 14:185–191
  14. Giacovazzo, M., Martelletti, P., Zaurito, V.: Piroxicam-beta-cyclodextrin in the treatment of headache
    acute analgesic effect and prevention of onset of headache attacks. Giorn. Neuropsicofarmacologia 1990; 12:27–33
  15. Davoli, L., Ciotti, G., Biondi, M., Passeri, M.: Piroxicam-beta-cyclodextrin in the treatment of low-back
    pain controlled study vs etodolac. Curr. Ther. Res. 1989; 46:940–947
  16. Bannwart, B., Bertin, P., Péhourcq, F., Schaeverbeke, T., Gillet, P., Lefrançois, G., Trèves, R., Dehais,
    J., Netter, P., Gaucher, A.: Piroxicam concentrations in plasma and synovial fluid after a single dose of
    piroxicam-beta-cyclodextrin. Int. J. Clin. Pharmacol. Ther. 2001; 39:33–36.

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