TOPICAL DOSAGE FORM OF LIPOSOMAL TETRACAINE - EFFECT OF ADDITIVES ON THE IN-VITRO RELEASE AND IN-VIVO EFFICACY

The drug release properties of four different topical liposomal tetracaine preparations were investigated in vitro using silastic membrane as a barrier in a flow-through diffusion cell system. The effect of formulation parameters and the presence of various additives such as methylcellulose, Carbopol, Veegum, Celtex 17 and gamma-linolenic acid, on the release kinetics from liposomes and on the topical anesthetic efficacy in volunteers was studied. The release of tetracaine from all liposomal formulations showed a similar triphasic profile. The total amount of tetracaine released from liposomes in 48 h and the amount of drug in peak sample is dependent on the composition and ranged from 18.9-51.5% and 31.9-65.8 mug/cm2, respectively. The presence of all the additives tested decreased both the total amount released and the amount of drug in peak sample with the exception of methylcellulose when used at concentrations below 3%. The appearance of peak was also delayed in the presence of most additives. Significantly higher amounts of tetracaine were released from the liposomal formulas than from the conventional ointments tested (PEG Ointment USP, Vaseline base, Glaxal base). In case of Glaxal base, however, similarly high amount of drug in peak sample could be achieved as with the liposome formulas. Studies in volunteers showed correlation between the efficacy and the amount of drug in peak sample. It was found that generally the lower the amount of drug in peak sample the weaker the anesthetic effect. The results of this study will contribute to the characterization of liposomes as a topical pharmaceutical dosage form and to the issues of bioavailability and bioequivalency of topical products in general.