Preparation and evaluation of bioadhesive dibucaine gels for enhanced local anesthetic action.
In relieving local pains, dibucaine, one of ester type local anesthetics, has been used. In case of their application such as ointments and creams, it is difficult to expect their effects for a required period of time, because they are easily removed by wetting, movement and contacting. To develop suitable bioadhesive gels, the bioadhesive force of hydroxypropyl cellulose (HPC) was tested using auto-peeling tester. The effect of drug concentration on drug release was studied from the prepared 2% HPC-HF gels using synthetic cellulose membrane at 37 +/- 0.5 degrees C. We investigated the enhancing effects on drug permeation into skins, using some kind of enhancers such as the glycols, the non-ionic surfactants, the fatty acids, and the propylene glycol derivatives. Anesthetic effects of dibucaine gels containing polyoxyethylene 2-oleyl ether were measured by tail flick analgesic meter. The bioadhesive force of various types of HPC such as GF, MF, and HF, was 0.0131, 0.0501, and 0.1346 N, at 2% HPC concentration, respectively. The HPC-HF gels showed the highest bioadhesive force. As the concentration of HPC-HF increased, the drug release increased. As the temperature increased, the drug release increased. Among the enhancers used, polyoxyethylene 2-oleyl ether showed the highest enhancing effects. According to the rat tail flick test, 1% drug gels containing polyoxyethylene 2-oleyl ether showed the prolonged local anesthetic effects. In conclusion, the dibucaine gel containing penetration enhancer and vasoconstrictor showing enhanced local anesthetic action could be developed by using the bioadhesive polymer, HPC.
Kang
Chung
C
College of Pharmacy, Chonnam National University, Gwangju, 500-757, Korea.
Shin
Sang-Chul
SC
D000268:Adhesiveness; D000279:Administration, Cutaneous; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D003992:Dibucaine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005079:Excipients / Q000737:chemistry; D005782:Gels; D008297:Male; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement; D051381:Rats; D017207:Rats, Sprague-Dawley; D012869:Skin Absorption; D013696:Temperature
D000779:Anesthetics, Local; D005079:Excipients; D005782:Gels; C508342:hydropropylcellulose; D002482:Cellulose; D003992:Dibucaine