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.
Formulation of a drug delivery system based on a mixture of monoglycerides and triglycerides for use in the treatment of periodontal disease.
This paper describes the development of a stable, controlled-release formulation of metronidazole for use in the treatment of periodontal disease. It is formulated as a suspension, which undergoes transformation to a release-controlling, semi-solid on contact with gingival fluid. The system is based on the ability of mixtures of monoglycerides and triglycerides to form liquid crystals, i.e., reversed hexagonals, in contact with water. The reversed hexagonal form was found to have the most favourable sustained release properties, compared with those from the cubic form. The source of metronidazole is the prodrug, metronidazole benzoate, which further helps to slow down the release rate. Product characteristics are assessed by differential scanning calorimetry and viscometry. The release data derive from the results of in vitro dissolution tests. X-ray diffraction, phase diagrams, and polarized light microscopy were used to elucidate the structure of the liquid crystalline phases.
Recalculation of Mass Defects
THE well-known mass defect curve of the old nuclear scheme calculated with regard to α-particles and protons presented a difficulty with its minimum of binding energy for tin and an increasing portion between tin and lead. On the other hand, the mass defect values against protons give a rather smoothly decreasing curve.1 As has already been pointed out,2 the number of α-particles must be considerably reduced from the point of view of the new scheme, which does not admit any electrons in nuclei, but only neutrons and protons (presumably joined as α-particles). The curve of mass defect against protons and neutrons (perhaps with a single ‘central’ α-particle) is very similar to the old curve against protons, but decreases less rapidly. Clearly the new mass defect values relatively to α-particles, neutrons and protons must lie somewhere between the old values computed relative to protons and α-particles respectively (because the number of α-particles is decreased). We may emphasise that this new mass defect curve shows no increasing portion between tin and lead. For illustration we give two typical values: Old: 50Sn124 = 31α + 12&#38;epsiv;; mass defect = 0.158 (in mass units); 82Pb208 = 52α + 22&#38;epsiv;; mass defect = 0.035. New: 50Sn124= 25α + 24ω (ω = neutron); mass defect = 0.304; 82Pb208 = 41α + 44ω; mass defect = 0.366.