*3.4.2. Sublingual*

A new sublingual administration system using sufentanil (AcelRx Pharmaceuticals, Redwood City, CA, USA) is designed as a microtablet coupled to a preprogrammed portable device with locking features and radio frequency identification to enable the characterization of a single user. Although intravenous sufentanil present a short half‐life context‐dependent due to its rapid redistribution, pharmacokinetic studies in healthy subjects showed that after sublingual administration, sufentanil has adequate profile for the postoperative analgesia [39].

Sufentanil NanoTabs® shows high bioavailability and plasma half‐life and it is safer than the administration of the drug intravenously to avoid the need for frequent administrations of the lipophilic opioids commonly used for this procedure. Several clinical trials have dem‐ onstrated its efficacy in pain relief in different types of orthopedic and abdominal surgery, having been described few side effects to this method [38].

#### *3.4.3. Inhalation*

Several products using the inhalation of PCA to opioid administration are described in the literature. Thipphawong et al. [63] tested a morphine inhalation system (System AERx Pain Management; Aradigma Corporation, Hayward, CA, USA), which had desirable character‐ istics of a drug for PCA (possibility of multiple dosing with lock time between them and observed similar efficacy to morphine IV‐PCA).

Similarly, fentanyl (AeroLEF, YM Biosciences, Mississauga, ON, Canada) also had proven to control postoperative pain following orthopedic surgery. However, further studies are needed to confirm the effectiveness of opioids in this route, especially clinical trials phase III and IV.

### *3.4.4. Intranasal*

The intranasal opioid administration is possible, since the nasal mucosa has an extensive vas‐ cularization, providing rapid drug absorption and distribution [12].

The presentation of intranasal morphine (Rylomine®, Javelin Pharmaceuticals Inc., Cambridge, MA, USA) was effective for the control of postoperative pain in orthopedic sur‐ gery [64]. However, the single dose after a nasal administration does not have the desirable safety features of PCA models, such as the possibility of multiple dosages and lock scheduled time between applications. Other opioids have been tested for intranasal administration but similar to morphine, these devices also did not have the desirable features of a PCA device. In this context, Toussaint et al. [65] noted that intranasal fentanyl administration showed similar efficacy compared to IV‐PCA fentanyl. Intranasal sufentanil was also successfully used both in adults and pediatric patients [64].

However, this route may have local adverse effects: nasal irritation, nasal congestion, upper respiratory tract infections, sinusitis, rhinitis, pharyngitis, or epistaxis, which may be a limitation of its clinical use [66].
