Preparation, characterization and in vivo efficacy evaluation of ropivacaine O/W emulsion by premix membrane emulsification

Ropivacaine (ROP), a new type of amide local anesthetic (LA) with low cardiac and neurotoxicity, is used to treat postoperative pain. However, ROP has a short half-life (t1/2 = 1.8 h) and the analgesic duration of a single-dose injection last only 3-4 h, which cannot meet clinical needs. In order to solve the problem, we combined an O/W emulsion method with a premix membrane emulsion technique to prepare sustained-release ropivacaine-loaded emulsion (ROP-E) with narrow droplets size distribution. As a result, the ROP-E about 8.385 mu m with a span value of 0.737 was obtained. Moreover, the sciatic nerve block model and the cutaneous trunci pinprick model were established to evaluate the efficacy of ROP-E in vivo. The results of the sciatic nerve model showed that the sensory nerve block duration (4.27 h) of ROP-E was significantly prolonged, which was 2.15 and 1.42 folds of ROP injection and Exparel (R) formulation, respectively. Similarly, the motor nerve block duration (3.62 h) was 1.8 and 1.46 folds of ROP injection and Exparel (R) formulation, respectively. Effective analgesia duration of ROP-E was about 18 h, 2.25 folds longer than that of ROP injection in the cutaneous trunci pinprick model. Besides, the ROP-E displayed excellent stability according to the droplet size, drug loading concentration, in vivo and in vitro release. H&E and blood biochemistry showed an insignificant difference between the ROP-E and the ROP injection, which further indicated the safety of ROP-E. These results suggested that ROP-E may be useful for sustained release of local anesthetics to prolong analgesia without causing systemic toxicity