title: Local anaesthetic block copolymer system undergoing phase transition on dilution with water.
abstract: The possibility of formulating a local anaesthetic system displaying in situ gelation on dilution with water, as well as its dependence on concentration of active ingredients and pH was investigated. For this purpose Lutrol F68, water, a eutectic mixture of lidocaine and prilocaine and Akoline MCM were mixed in different ratios and investigated using crossed polarisers, small-angle X-ray diffraction, rheology, conductivity and NMR self-diffusion measurements. In particular, an isotropic phase of low viscosity turning into a high viscous hexagonal phase upon dilution with water was found. The increase in viscosity is only weakly dependent on temperature in the temperature range of 20-37 degrees C. 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 investigated region. The in vitro release of lidocaine and prilocaine was found to increase with increasing concentration of the active ingredients and with decreasing pH, the latter as a consequence of the pH-dependent ionisation of these substances. The behaviour of the system is promising from a pharmaceutical point of view, since the isotropic low-viscous phase can be injected into, e.g. a periodontal pocket where the presence of saliva will cause a temporal transition into a rigid hexagonal phase thus making the formulation stay at the application site. At even higher water content, either as a result of longer application time or rinsing with water, the hexagonal phase is effectively dissolved through transformation to a water-rich micellar phase.
authors.affiliation: AstraZeneca R&D, SE-151 85, Södertälje, Sweden. marie.scherlund@astrazeneca.com
authors.forename: M
authors.initials: M
authors.lastname: Scherlund
authors.forename: K
authors.initials: K
authors.lastname: Welin-Berger
authors.forename: A
authors.initials: A
authors.lastname: Brodin
authors.forename: M
authors.initials: M
authors.lastname: Malmsten
mesh_terms: D000779:Anesthetics, Local / Q000008:administration & dosage* / Q000737:chemistry; D004058:Diffusion; D004548:Elasticity; D004553:Electric Conductivity; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D019999:Pharmaceutical Solutions; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers; D012212:Rheology; D012995:Solubility; D014867:Water; D014961:X-Ray Diffraction
chemical_list: D000779:Anesthetics, Local; D008823:Micelles; D019999:Pharmaceutical Solutions; D011108:Polymers; D014867:Water; D011092:Polyethylene Glycols