Celecoxib Oral Solution and the Benefits of Self-Microemulsifying Drug Delivery Systems (SMEDDS) Technology: A Narrative Review

Abstract

Introduction: The oral route of drug delivery is the most widespread and preferred route of administration, but it has several limitations, including variable pharmacokinetics (PK), reduced dissolution and absorption, and gastrointestinal irritation. Further, many compounds have low aqueous solubility, which also limits intestinal absorption.

Methods: For this narrative review, we conducted a literature search of PubMed until August 2022, focusing on emulsions, microemulsions, nanoemulsions, and self-emulsifying drug delivery systems.

Results: The self-microemulsifying drug delivery system (SMEDDS) overcomes these limitations of hydrophobic compounds to enhance their bioavailability. A SMEDDS formulation is a clear, thermodynamically stable, oil-in-water emulsion of lipid, solubilized drug, and two surfactants, which spontaneously forms droplets < 100 nm in diameter. These components help deliver presolubilized drugs to the gastrointestinal tract, while protecting them from degradation in gastric acid or first-pass hepatic metabolism. SMEDDS formulations have improved oral drug delivery in the treatment of cancer (paclitaxel), viral infections (ritonavir), and migraine headache (ibuprofen and celecoxib oral solution). The American Headache Society recently updated their consensus statement for the acute treatment of migraine and included a selective cyclo-oxygenase-2 selective inhibitor formulated in SMEDDS, celecoxib oral solution. This SMEDDS formulation showed pronounced improvement in bioavailability compared with celecoxib capsules, allowing for a low dose of celecoxib in the oral solution to provide safe and effective acute migraine treatment. Here, we will focus on SMEDDS formulations, what differentiates them from other analogous emulsions as vehicles for poorly soluble drugs, and their clinical application in the acute treatment of migraine.

Conclusions: Oral drugs reformulated in SMEDDS have shown accelerated times to peak plasma drug concentrations and increased maximum plasma concentrations, compared with capsules, tablets, or suspensions. SMEDDS technology increases both drug absorption and bioavailability of lipophilic drugs, compared with other formulations. Clinically, this allows the use of lower doses with improved PK profiles without compromising efficacy, as shown with celecoxib oral solution for the acute treatment of migraine.

Keywords: COX-2 inhibitor; Cyclo-oxygenase-2 inhibitors; Microemulsion; Migraine; Nonsteroidal anti-inflammatory drugs; Self-emulsifying drug delivery system; Self-nanoemulsifying drug delivery system.

Fig. 1

Mean plasma concentration of celecoxib oral solution (DFN-15) compared with celecoxib capsules from A 0–72 h and B 0–3 h. This figure was modified from Pal et al. Clin Drug Investig. 2017 [52] under CC BY-NC 4.0 license terms [http://creativecommons.org/licenses/by-nc/4.0/]

Fig. 2

Proportion of patients from two clinical trials reporting headache pain relief at sequential time points after dosing of 120 mg of celecoxib oral solution. This figure was modified from Lipton et al. Headache 2020 [53] and Lipton et al. J Pain Res. 2021 [54] (excluding data from the outlier site) under CC BY-NC 4.0 license terms [http://creativecommons.org/licenses/by-nc/4.0/]