# The Use of Ibuprofen Arginate in Pain Management Following Third Molar Surgery--A Scoping Review
## 1 Introduction  
Third molar extractions can be considered one of the most common oral surgery procedures and may lead to severe postoperative pain, significantly affecting patients' quality of life [1, 2]. To avoid postoperative pain, pharmacological painkillers are divided into two major categories: opioid analgesics, which work exclusively on the central nervous system, at opioid receptor sites, and non-opioid analgesics, which include non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen [3, 4].  
Ibuprofen is a propionic acid derivative with non-steroidal anti-inflammatory analgesic and antipyretic properties [5]. The primary analgesic mechanism of ibuprofen, like other NSAIDs, involves reducing the hyperalgesia associated with tissue damage. Thiseffect is achieved by competing with arachidonic acid for cyclooxygenase (COX) enzymes, thereby inhibiting the production of inflammatory and hyperalgesic prostaglandins in peripheral tissues [4; 6; 7; 8]. Ibuprofen is a racemic mixture that contains both R(\(-\)) and S(+) enantiomers. The inhibition of cyclooxygenase due to the S(+) enantiomer leads to anti-inflammatory, analgesic, and anti-platelet effects [9; 10; 11]. On the other hand, the R(\(-\)) enantiomer is less effective at inhibiting prostaglandin (PG) synthesis, but it still possesses certain pharmacological properties that contribute to the overall anti-inflammatory effect [12]. However, after oral absorption, in the intestinal tract and liver, 50-60% of the R(\(-\)) enantiomer of ibuprofen is metabolically converted into the S(+) form [13; 14].  
Regarding the oral formulations of ibuprofen, they are highly effective within a dose range of 200-800 mg, with a maximum total daily dose of 3200 mg. The 800 mg dose provides maximum analgesic effects, but clinicians should only consider it when the benefits of treating severe pain outweigh the increased risks of adverse effects. In fact, under most circumstances, a dosage of 400 or 600 mg taken every 6 h is quite effective against moderate inflammatory pain [15]. In fact, there have been conflicting results concerning the optimal dosing regimen and timing of administration of oral ibuprofen [16].  
Ibuprofen is rapidly absorbed by the upper gastrointestinal tract, with a time to reach the maximum concentration (Cmax) (Tmax) of less than 0.25 h for granules and approximately 2 h for tablets. However, absorption can be delayed when ibuprofen is taken with food [17]. The plasma S/R ratio is influenced by the drug's release characteristics, with sustained-release formulations exhibiting higher ratios than immediate-release formulations [14]. Analgesic effects typically begin within 1 h of administration or less, and the duration of action for the drug is at least 6 to 8 h [5; 18; 19; 20].  
The bioavailability of ibuprofen, which is a weak acid, is enhanced through salification with agents such as lysine, sodium, and arginine. Several products currently available on the market contain salified forms of ibuprofen, with a reduced Tmax and an increased Cmax compared to the free-acid form [21; 22; 23; 24].  
Ibuprofen arginate is produced by bonding racemic ibuprofen to the amino acid L-arginine [25; 26], and this could subsequently impact the level of inversion, the availability of the active S-(+) enantiomer in the body, and the overall therapeutic effectiveness of ibuprofen [26].  
Salifying ibuprofen with arginine appears to enhance its pain relief effectiveness and speed up its action, thanks to its improved solubility and quicker absorption through the stomach and intestinal tract [27; 28].  
In this regard, it could be interesting to understand whether ibuprofen arginate could offer any advantages in patient recovery after third molar surgery.  
The aim of this scoping review was to assess the current state of knowledge regarding the use of ibuprofen arginate for managing postoperative inflammation after third molar extraction, in comparison to conventional ibuprofen.