In vitro cutaneous and percutaneous delivery and in vivo efficacy of tetracaine from liposomal and conventional vehicles.

The aim of this study was to quantitate drug delivery and correlate drug concentration in the skin with anesthetic effect. The rate of delivery of radiolabelled tetracaine from two different liposome formulas (1F2 and 23C2) and two conventional dosage forms (PEG Ointment USP and Glaxal base) was investigated in Flow-thru diffusion cells using human breast skin from mammoplasty. The results indicated a 1.5 and 4 times higher concentration of tetracaine within the skin when the liposomal formula (1F2) was used, compared to tetracaine in Glaxal base and PEG Ointment USP, respectively. The amount of drug delivered into the skin in 24 h from the liposomal formula was 5.3% of total applied whereas from Glaxal base it was 3.3% and from PEG Ointment base it was 1.2%. The amount of liposomal (1F2) phospholipids in the skin after 24h was 68.3 micrograms/cm2 (0.2% of total applied). The steady state flux of tetracaine from liposomes (1F2) was 16.06 micrograms/cm2/h with a lag time of 3.1h, from Glaxal base 10.24 micrograms/cm/h with a lag time of 11.2h and from PEG Ointment it was 5.70 micrograms/cm2/h with a lag time of 9.0h. The second liposome formula (23C2) showed similar flux and permeability coefficient than the Glaxal base, however the lag time was about half. The results indicated that optimized liposome formulation is necessary to achieve maximum drug delivery. The concentration of drug within the skin and the flux measured in vitro showed correlation with in vivo efficacy. The in vivo data showed that liposomal (1F2) tetracaine produced the deepest anesthesia with shortest onset in volunteers, followed by Glaxal base, liposome formula 23C2 while tetracaine in PEG Ointment had a lack of effect.