The Study On Topical Lidocaine Gel

ABSTRACT Lidocaine is a local anesthetic of amide type and traditionally regarded as one of the most potent local anesthetics with the advantages of good pbysicochemical stability, rapid onset and long duration. Injection and 5% mucilage of Lidocaine hydrochloride (LH) are the main dosage forms used in domestic clinical practice, there are also tapes, aerosols, creams and gels for the local anesthesia of mucous membrane and skin marketed in other countries. In the preformulation experiments, pKa of LH at 320C was determined by potentiometry and the effect of pH on the permeation of LH was investigated. The steady state flux (J~) at different pH was determined with improved Valia- Chien diffusion cell. The profile of J~ versus pH showed a 揝?shaped curve. J~ was very small when pH was lower than pKa and increased substantially when pH was close to pKa and showed a slow rise with the increase of pH when pH was higher than pKa. Lag time was shortened obviously when pH was higher than pKa. In addition, the permeations of LH at pH 9.00 of seven kinds of enhancers in their common concentrations were evaluated and compared. The enhancement of oil-soluble enhancers was better than that of water-soluble enhancers, while the latter, but not the former could shorten the lag time of Lidocaine. On the basis of the studies mentioned above, the formulation of Lidocaine gel was optimized by orthogonal design experiment. The stability study of Lidocaine gel showed that the drug content, the release of Lidocaine and the permeation across rat skin of gel had no obvious changes in accelerated and long-term experiment. The results of irritation experiment demonstrated that Lidocaine gel had no irritation to intact skin and middle irritation to damaged skin. In this thesis, cutaneous microdialysis was used to investigate the percutanous absorption of Lidocaine gel. The peak of drug concentration in dialysate occurred at 1.25h or so. Pharmacological action of Lidocaine gel was evaluated 3 and compared with that of EMLA cream. It was found that Lidocaine gel had nearly same onset time with EMLA, but its anesthetic duration and anesthetic action were better than those of the latter.