Development and characterization of PLGA-Bupivacaine and PLGA-S75:R25 Bupivacaine (Novabupi®) biodegradable implants for postoperative pain

Abstract In the hospital environment, postoperative pain is a common occurrence that impairs patient recovery and rehabilitation and lengthens hospitalization time. Racemic bupivacaine hydrochloride (CBV) and Novabupi® (NBV) (S (-) 75% R (+) 25% bupivacaine hydrochloride) are two examples of local anesthetics used in pain management, the latter being an alternative with less deleterious effects. In the present study, biodegradable implants were developed using Poly(L-lactide-co-glycolide) through a hot molding technique, evaluating their physicochemical properties and their in vitro drug release. Different proportions of drugs and polymer were tested, and the proportion of 25%:75% was the most stable for molding the implants. Thermal and spectrometric analyses were performed, and they revealed no unwanted chemical interactions between drugs and polymer. They also confirmed that heating and freeze-drying used for manufacturing did not interfere with stability. The in vitro release results revealed drugs sustained release, reaching 64% for NBV-PLGA and 52% for CBV-PLGA up to 30 days. The drug release mechanism was confirmed by microscopy, which involved pores formation and polymeric erosion, visualized in the first 72 h of the in vitro release test. These findings suggest that the developed implants are interesting alternatives to control postoperative pain efficiently.

摘要：在医院场景中，术后疼痛是一类常见病症，会损害患者的康复进程并延长住院时长。消旋盐酸布比卡因（Racemic bupivacaine hydrochloride, CBV）与Novabupi®（NBV，即S(-)构型占75%、R(+)构型占25%的盐酸布比卡因）是两种用于疼痛管理的局部麻醉剂，后者是一种不良反应更为轻微的替代方案。本研究采用热成型工艺，以聚(L-乳酸-共-乙醇酸)（Poly(L-lactide-co-glycolide, PLGA)）为载体制备了可生物降解植入剂，并对其理化性质与体外释药行为开展评价。研究测试了不同药物与聚合物的配比，其中25%:75%的配比最适于植入剂的成型。热分析与光谱分析结果显示，药物与聚合物之间未出现不良化学相互作用，同时证实制备过程中采用的加热与冷冻干燥工艺不会干扰药物稳定性。体外释药结果表明药物呈持续释放特性：至30天时，NBV-PLGA组释药率可达64%，CBV-PLGA组可达52%。通过显微镜观测证实，该释药机制为孔隙形成与聚合物侵蚀，该现象可在体外释药试验的前72小时内被观测到。上述研究结果表明，本研究开发的植入剂有望成为高效控制术后疼痛的优质替代方案。