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

Int J Pharm. 2014 Dec 30;477(1-2):47-56. doi: 10.1016/j.ijpharm.2014.10.005. Epub 2014 Oct 7.

Abstract

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.

Keywords: Analgesic activity; Carbopol; Microemulsion; Ropivacaine; Transdermal delivery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Cutaneous
  • Amides / administration & dosage*
  • Amides / pharmacokinetics
  • Amides / pharmacology
  • Anesthetics, Local / administration & dosage*
  • Anesthetics, Local / pharmacokinetics
  • Anesthetics, Local / pharmacology
  • Animals
  • Chemistry, Pharmaceutical
  • Disease Models, Animal
  • Emulsions
  • Excipients / chemistry*
  • Gels
  • Male
  • Mice
  • Microscopy, Electron, Transmission
  • Particle Size
  • Ropivacaine
  • Skin Absorption*
  • Solubility

Substances

  • Amides
  • Anesthetics, Local
  • Emulsions
  • Excipients
  • Gels
  • Ropivacaine