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 Table of Contents    
Year : 2022  |  Volume : 54  |  Issue : 4  |  Page : 297-298

Celecoxib-tramadol co-crystal: Efficacy in acute postoperative pain

Department of Anaesthesiology, Ibra Hospital, Ministry of Health-Oman, Ibra, Oman

Date of Submission22-Feb-2022
Date of Decision08-Aug-2022
Date of Acceptance24-Aug-2022
Date of Web Publication04-Oct-2022

Correspondence Address:
Dr. Abhijit Sukumaran Nair
Department of Anaesthesiology, Ibra Hospital, Ministry of Health-Oman, P. O. Box: 275, Ibra-414
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijp.ijp_141_22

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How to cite this article:
Nair AS. Celecoxib-tramadol co-crystal: Efficacy in acute postoperative pain. Indian J Pharmacol 2022;54:297-8

How to cite this URL:
Nair AS. Celecoxib-tramadol co-crystal: Efficacy in acute postoperative pain. Indian J Pharmacol [serial online] 2022 [cited 2022 Dec 3];54:297-8. Available from: https://www.ijp-online.com/text.asp?2022/54/4/297/357826


Acute postoperative pain is a situation that requires more than one medication with a different mechanism of action, also referred to as multimodal analgesia. In order to acquire therapeutic benefits, co-crystal medicines, which include two or more active ingredients, were developed to address the physicochemical limitations of each drug. By adding an appropriate therapeutically beneficial component without any chemical alteration, these co-crystals have better physicochemical and biologic properties of medication, are cost-efficient, and have low risk.

Celecoxib-tramadol co-crystal (CTC) consists of two commonly used analgesics. The co-crystal is a tablet composition and comprises 44 mg of tramadol and 56 mg of celecoxib (available as 100 mg tablet). This is an instant release formulation that combines celecoxib with racemic tramadol hydrochloride in a molecular ratio of 1:1. Celecoxib is a selective cyclo-oxygenase-2 inhibitor and tramadol acts by μ-opioid receptors agonism and also by the inhibition of the reuptake of norepinephrine and serotonin.

Cebrecos et al. compared the pharmacokinetic characteristics of CTC with the tramadol and celecoxib products available in the United States in a 4-way crossover randomized research comparing bioavailability that involved 36 healthy volunteers which were divided into four groups.[1] Group 1 received 200 mg CTC (112 mg of celecoxib and 88 mg of tramadol). Groups 2 and 3 also received 200 mg CTC, along with 100 mg of tramadol and 100 mg of celecoxib. Group 4 also received a dose of celecoxib100 mg and tramadol 200 mg. Following investigation, the authors came to the conclusion that co-crystallization had a favorable effect on the pharmacokinetic parameters of each active component in CTC and did not cause a higher level of systemic exposure when compared to celecoxib, tramadol, and their concurrent administration on the US market. In a study involving 36 healthy volunteers, Encina et al. reported that when given in co-crystal formulation to healthy volunteers, food intake increased the bioavailability of celecoxib but did not affect the bioavailability of tramadol.[2] The co-crystal analgesia has demonstrated better efficacy due to faster absorption of celecoxib and slower absorption of tramadol when compared to the absorption profile when administered separately.[3]

Three hundred and thirty-four patients undergoing tooth extraction with bone removal participated in a phase II dose-finding, randomized, double-blind, placebo-and active-controlled, multicenter research. The recruited patients received 50, 100, 150, or 200 mg of CTC in comparison to 100 mg of tramadol or placebo. On analysis, the authors concluded that there was significant pain relief in patients who received CTC when compared to patients who received 100 mg tramadol and placebo for managing acute postoperative pain.[4] Videla et al. demonstrated that the pharmacokinetic parameters of each component of the co-crystal get modified when administered in single or multiple doses when compared to celecoxib and tramadol alone or in combination.[5]

The US Food and Drug Administration recently approved CTC for the treatment of acute postoperative pain. A dose ranging from 100 to 200 mg twice daily is recommended and should be advised at the clinician's discretion. Currently, the co-crystal is marketed by ESTEVE pharmaceuticals (Barcelona, Spain) under the brand name Seglentis. Further comparative studies are required to establish its safety and efficacy in various surgical indications.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Cebrecos J, Carlson JD, Encina G, Lahjou M, Sans A, Sust M, et al. Celecoxib-tramadol co-crystal: A randomized 4-way crossover comparative bioavailability study. Clin Ther 2021;43:1051-65.  Back to cited text no. 1
Encina G, Encabo M, Escriche M, Lahjou M, Sicard E, Smith K, et al. The effect of food on tramadol and celecoxib bioavailability following oral administration of Co-Crystal of Tramadol-Celecoxib (CTC): A randomised, open-label, single-dose, crossover study in healthy volunteers. Clin Drug Investig 2018;38:819-27.  Back to cited text no. 2
Gascon N, Almansa C, Merlos M, Miguel Vela J, Encina G, Morte A, et al. Co-crystal of tramadol-celecoxib: Preclinical and clinical evaluation of a novel analgesic. Expert Opin Investig Drugs 2019;28:399-409.  Back to cited text no. 3
López-Cedrún J, Videla S, Burgueño M, Juárez I, Aboul-Hosn S, Martín-Granizo R, et al. Co-crystal of tramadol-celecoxib in patients with moderate to severe acute post-surgical oral pain: A dose-finding, randomised, double-blind, placebo- and active-controlled, multicentre, phase II trial. Drugs R D 2018;18:137-48.  Back to cited text no. 4
Videla S, Lahjou M, Vaqué A, Sust M, Escriche M, Soler L, et al. Pharmacokinetics of multiple doses of co-crystal of tramadol-celecoxib: Findings from a four-way randomized open-label phase I clinical trial. Br J Clin Pharmacol 2018;84:64-78.  Back to cited text no. 5


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