Toward Opioid-Sparing Oral Surgery: Does Intra-Socket Delivery of a Biodegradable Extended-Release Bupivacaine Hydrogel Enhance Postoperative Analgesia After Impacted Mandibular Third Molar Surgery?

Introduction and Aims: Postoperative pain after mandibular third molar extraction often leads to systemic NSAID or opioid use, risking adverse effects and overuse. This study aimed to develop and evaluate a degradable Bupivacaine/Carbopol hydrogel for sustained pain relief after third molar surgery. Methods: A single-center, double-blinded, split-mouth randomized clinical trial was conducted at the Qazvin University of Medical Sciences outpatient clinic. Sixteen adult patients (8 males, 8 females; mean age 24.3 ± 3.1 years) with bilaterally impacted mandibular third molars participated. Intra-socket injections of Bupivacaine/Carbopol hydrogel versus placebo were administered post-operatively. Pain intensity was self-reported on a 10-point visual analog scale (VAS) at 0, 2, 6, 12, 24, and 72 hours post-surgery; daily analgesic (NSAID/opioid) consumption was recorded for three days. Repeated-measures ANOVA using SPSS v24, with α = 0.05, was employed. Results: Significant main effects of time, group, and their interaction on VAS scores were observed (all P < 0.05). Except at 2 hours, the hydrogel group experienced significantly lower pain levels at 6, 12, 24, and 72 hours compared to the placebo. No significant differences in daily analgesic intake between groups over time were found (P > 0.05). Conclusions: The localized, degradable Bupivacaine/Carbopol hydrogel offers sustained postoperative pain relief and could decrease dependence on systemic painkillers in oral surgery. Larger clinical trials are necessary to confirm these findings and optimize the formulation. Trial Registration The study was conducted in accordance with the WMA Declaration of Helsinki and approved by the Research Ethics Committee of Qazvin University of Medical Sciences (approval ID: IR.QUMS.REC.1402.102) and the Iranian Registry of Clinical Trials (approval ID: IRCT20221201056682N1, 2023-07-17).