Concentration-response analysis of percutaneous local anaesthetic formulations

The percutaneous absorption of amethocaine has been measured for different concentrations of the drug in three different formulations, A, B and C. Statistical analysis indicated that a concentration of 4% produced effective percutaneous local anaesthesia to pin-prick, together with an acceptable onset time of approximately 40 min. Increasing the concentration did not reduce the onset time further, although there was some increase in the duration of anaesthesia. Formulations A and B were hydrophilic, whereas C was an oil-in-water cream. Effective anaesthesia with formulation C required a higher drug concentration (12%), perhaps because of partitioning of the lipophilic anaesthetic into the lipid phase of the vehicle. The rate-limiting step was considered to be diffusion by the lipophilic anaesthetic through the stratum corneum, shown by onset of anaesthesia after removal of the formulation from the test site.