In situ gelling drug delivery systems for periodontal anaesthesia.
In this thesis local anaesthetic formulations based on PEO-PPO-PEO block copolymers (PEO and PPO being poly(ethylene oxide) and poly(propylene oxide), respectively) or nonionic cellulose ethers undergoing temperature- or dilution-induced thickening were investigated. The aim of the work was to develop formulations which can be easily administered to the periodontal pocket, stay at the application site, give a fast onset of anaesthesia and have a duration sufficient to perform periodontal scaling procedures. Emulsions, (mixed) micellar solutions and microemulsions fulfilling the requirements stated above were achieved by combining the active ingredients lidocaine and prilocaine with the nonionic block copolymers Lutrol® F127 and Lutrol® F68. The critical micellisation and gelation temperatures of the systems were found to be interconnected and influenced by the total polymer concentration and the polymer mixture composition, as well as the presence of cosolutes and pH. A low-viscous isotropic phase that turns into a high-viscous hexagonal phase as the water content increases was found by combining Lutrol® F68, water, a eutectic mixture of lidocaine and prilocaine and Akoline MCM. The system has a slower release rate compared to the microemulsion formulation which might make it suitable for indications where a longer duration is needed. Finally, a temperature-induced gelling system was achieved by adding lidocaine and prilocaine to mixtures of ethyl(hydroxyethyl)cellulose (EHEC) and sodium dodecyl sulfate (SDS), hexadecyltrimethylammonium bromide (CTAB) or myristoylcholine bromide systems at, or just below, the surfactant concentration found to give a maximum viscosity increase at room temperature. In particular, the myristoylcholine bromide system may be interesting considering its antibacterial properties and biodegradability.
In situ forming lyotropic liquid crystalline systems containing metronidazole-benzoate
Lyotropic liquid crystals are usually formed from water and one or two surfactants and possibly cosurfactants and oils within a definite concentration and temperature range. The aim of this study was to evaluate self-forming lyotropic liquid crystalline systems for pharmaceutical use, which consist of oils and surfactants with good physiological tolerance and possess a suitable drug release profile. For determining the liquid crystalline structure, polarization microscopy and rheological examinations were used. The drug release studies were performed in vitro with a vertical diffusion cell. Based on the structure examinations it can be stated that the investigated water-free compositions turn spontaneously into high-viscous lyotropic liquid crystalline systems by water absorption, in this way they are proper formulations for in situ gelling drug delivery systems. On the basis of the drug release examinations we can conclude that a considerable amount of the drug was released in the course of the examination and the chemical entity of the surfactant exerted major influence on drug liberation.
SR topography of plastically deformed Fe-Si bicrystals - observation in situ and post mortem
SR reflection topography was applied to study the interaction of slip dislocations with the grain boundaries in Fe-4at%Si bicrystals deformed by compression. Three experimental settings with either a white or monochromatic beam were used and the corresponding orientation contrast analysed. Dislocation transmission through the grain boundary was observed in bicrystals with favourable geometry of the slip systems.