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

Abstract

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 µm 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® formulation, respectively. Similarly, the motor nerve block duration (3.62 h) was 1.8 and 1.46 folds of ROP injection and Exparel® 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.