Preparation and characterization of two-phase melt systems of lidocaine

Abstract

The melting point of lidocaine was significantly lowered when mixed with thymol and/or aqueous ethanol. Mixtures of lidocaine and thymol at ratios within the range of 30:70–70:30 (w:w) became homogeneous oils at 25°C. In a pH 9.2 carbonate buffer containing 25% ethanol, lidocaine (5%, w:w) also liquefied at 25°C. The studies led to the development of novel two-phase melt systems of lidocaine (TMS) which consisted of a highly concentrated oil phase of lidocaine and an alcoholic aqueous phase. A compositional phase diagram showed that in aqueous dispersions of lidocaine, concurrent use of thymol and ethanol depressed the melting point of lidocaine more effectively than when they were used individually. Both thymol and aqueous ethanol were necessary as melting point depressing agents to achieve the highest possible lidocaine concentration of 87% (w:w) in the oil phase of a TMS at 25°C. Containing an internal oil phase and an external aqueous phase at ambient temperature, such a TMS can be readily formulated into topical O/W cream after addition of proper surfactants and thickening agents. In an anesthetic activity test 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).