Preparation and characterization of two-phase melt systems of lidocaine

The melting point of lidocaine was significantly lowered when mixed with th ymol and/or aqueous ethanol. Mixtures of lidocaine and thymol at ratios wit hin the range of 30:70-70:30 (w:w) became homogeneous oils at 25 degreesC. In a pH 9.2 carbonate buffer containing 25% ethanol, lidocaine (5%, w:w) al so liquefied at 25 degreesC. The studies led to the development of novel tw o-phase melt systems of lidocaine (TMS) which consisted of a highly concent rated oil phase of lidocaine and an alcoholic aqueous phase. A compositiona l phase diagram showed that in aqueous dispersions of lidocaine, concurrent use of thymol and ethanol depressed the melting point of lidocaine more ef fectively than when they were used individually. Both thymol and aqueous et hanol were necessary as melting point depressing agents to achieve the high est possible lidocaine concentration of 87% (w:w) in the oil phase of a TMS at 25 degreesC. Containing an internal oil phase and an external aqueous p hase at ambient temperature, such a TMS can be readily formulated into topi cal O/W cream after addition of proper surfactants and thickening agents. I n an anesthetic activity lest using mouse tail-flick model, a 5% lidocaine cream prepared was highly effective as shown by the prolonged latency time of the mice to a heat stimulus as compared with a placebo (P <0.05). (C) 20 01 Elsevier Science B.V. All rights reserved.