Ropivacaine loaded microemulsion and microemulsion-based gel for transdermal delivery: preparation, optimization, and evaluation.

The objective of the present study was to prepare and evaluate a ropivacaine-loaded microemulsion (ME) formulation and microemulsion-based Carbopol gel (ME-gel) for transdermal delivery. Pseudo-ternary phase diagrams and a simplex lattice experiment design were utilized to screen and optimize the ME formulation. In the process, drug solubility and particle size were inspected as dependent variables whilst Capryol(®) 90 (X1), Smix (X2, Labrasol(®): absolute ethanol=1:2 w/w), water (X3) as independent variables. Following the optimization, the optimal ME formulation was comprised of 15% Capryol(®) 90, 53% Smix, and 32% water, respectively. Ropivacaine loaded ME appeared to be spherical under transmission electron microscope, and the average particle size was 58.79 nm. The results of ex vivo permeation study showed that ropivacaine had a significant higher cumulative amount from ME than that from ME-gel. Histopathology study elucidated that the microstructure of skin surface was significantly changed by the treatment of ME formulation. Skin irritation study indicated that neither ME nor ME-gel caused any irritation responses. Both ME and ME-gel presented a remarkable analgesic activity on acetic acid-induced writhing in mice. In conclusion, ME could be a promising formulation for ropivacaine transdermally administration.