Formulation of vesicular nano-invasomes for simultaneous topical delivery of Bupivacaine and Buprenorphine

Abstract

Introduction: Different types of invasive procedures like intravenous catheter insertion are painful operations. Therefore, pain management is an essential step in these procedures. Available anesthetic formulations cause insufficient anesthesia with a long onset time. Lipid nano-carriers are very effective in facilitating skin permeability. Among lipid nanocarriers, invasomes offer high skin permeability due to their unique structure. Aims: Preparation of topical analgesic formulation containing two strong analgesics from two different groups that are simultaneously loaded in a system with high skin permeability to provide a formulation with rapid onset time. Methods: First, the DOE test was performed to design an ideal formulation. Then, the formulation was examined for size and encapsulation efficiency. The properties of vesicles were investigated using TEM, XRD and FTIR techniques. Finally, in-vitro skin permeability studies were performed using franz diffusion cell apparatus and fluorescence microscopy. Also, the quality of analgesia was evaluated by tail flick test in in-vivo studies. Results: In this study, the ideal formulation with 2% terpene (menthol) was obtained with particle size of 0.99 ± 0.18 µm and encapsulation efficiency of 97.53 ± 1.43 and 92.14 ± 0.45 and loading capacity of 19.5 ± 0.96 and 18.4 ± 0.19 for buprenorphine and bupivacaine, respectively. Studies by franz cell, fluorescence microscopy and tail flick test showed better skin penetration and more effective analgesia for invasome than controls. Conclusion: Invasome nano-carriers have high skin permeability, so they provide a suitable carrier for analgesics with rapid access to pain receptors in the skin.