Development of the Bioadhesive Tetracaine Gels for Enhanced Local Anesthetic Effects

Abstract

To develop the new local anesthetic formulations with a suitable bioadhesive property, hydroxypropyl methylcellulose (HPMC)‐based gel was formulated. As the drug concentration in the gels, and the temperature of surrounding solutions increased, the drug release increased. The activation energy of tetracaine permeation was 4.47 kcal/mol. The effects of permeation enhancers on the permeation rate of drug through skin were studied using various enhancers, such as the glycols, the nonionic surfactants, and the bile salts. Among the enhancers used, polyoxyethylene 2‐oleyl ether showed the highest enhancing effects on drug permeation through skin. The analgesic activity was examined using a tail‐flick analgesimeter. In the AUEC (area under the efficacy curve) of the rat‐tail flick test, tetracaine gel containing polyoxyethylene 2‐oleyl ether showed about 3.2‐fold increase in analgesic activity compared with the control. The results of this study support that the tetracaine gels with efficient anesthetic effects could be developed using HPMC and poloxamer with combination of enhancer and vasoconstrictor.

Key Words:

• Local anesthetics
• Hydroxypropyl methylcellulose
• Tetracaine
• Gels
• Enhancer
• Tail flick