Local anaesthetic block copolymer system undergoing phase transition on dilution with water

The possibility of formulating a local anaesthetic system displaying in sit u gelation on dilution with water, as well as its dependence on concentrati on of active ingredients and pH was investigated. For this purpose Lutrol ( R) F68, water, a eutectic mixture of lidocaine and prilocaine and Akoline M CM were mixed in different ratios and investigated using crossed polarisers , small-angle X-ray diffraction, rheology, conductivity and NMR self-diffus ion measurements. In particular, an isotropic phase of low viscosity turnin g into a high viscous hexagonal phase upon dilution with water was found. T he increase in viscosity is only weakly dependent on temperature in the tem perature range of 20-37 degreesC. The rheology and in vitro drug release of these systems were studied and the elastic modulus was found to be fairly independent of concentration of active ingredients and pH in the investigat ed region. The in vitro release of lidocaine and prilocaine was found to in crease with increasing concentration of the active ingredients and with dec reasing pH, the latter as a consequence of the pH-dependent ionisation of t hese substances. The behaviour of the system is promising from a pharmaceut ical point of view, since the isotropic low-viscous phase can be injected i nto, e.g. a periodontal pocket where the presence of saliva will cause a te mporal transition into a rigid hexagonal phase thus making the formulation stay at the application site. At even higher water content, either as a res ult of longer application time or rinsing with water, the hexagonal phase i s effectively dissolved through transformation to a water-rich micellar pha se. (C) 2001 Elsevier Science BY. All rights reserved.