Sustained delivery of prilocaine and lidocaine using depot microemulsion system: in vitro, ex vivo and in vivo animal studies

• Published in: Drug development and industrial pharmacy 2020-02, Vol.46 (2), p.264-271
• Main Authors: Zhang, Xiaomin, Dang, Minyan, Zhang, Wenzhi, Lei, Yan, Zhou, Wentao
• Format: Article
• Language: English
• Subjects: animal study; ex vivo study; lidocaine; Local anesthesia; microemulsion; prilocaine
• ISSN: 0363-9045; 1520-5762
• DOI: 10.1080/03639045.2020.1716377

Topical drug delivery for local anesthetics has been an interesting area of research for formulators considering the resistance and barrier properties of skin and high clearance rate of drugs like prilocaine and lidocaine (duration of action < 2.5 h). In this study, efforts have been made to sustain the release of prilocaine and lidocaine by using depot microemulsion system. Drug loaded microemulsions were formulated using Capmul MCM, Pluronic F127, polyethylene glycol 200 (PEG 200) and water from pseudo-ternary diagrams. The S mix at 1:4 ratio showed larger microemulsion area in comparison to 1:2 ratio. The ex-vivo studies indicate sustained release of prilocaine and lidocaine from the microemulsion up to 8 h, in comparison to 4 h with ointments. Skin irritation study on rabbits confirmed the safety of drug loaded microemulsions for local drug delivery. The improved ex vivo data is reflected in the in vivo studies, were radiant heat tail-flick test and sciatic nerve model showed prolong duration of action for both prilocaine and lidocaine microemulsions in comparison to ointment. The in vitro and in vivo efficacy of prilocaine and lidocaine was non-significant. The improved efficacy was due to high penetration of microemulsion and depot effect due to local precipitation (destabilization of microemulsion) of drug in the skin layer. The sustained local anesthetic effect is highly desirable for the treatment of skin irritation due to skin burns and pre- and post-operative pain.