Micellization and gelation in block copolymer systems containing local anesthetics.
A formulation consisting of a eutectic mixture of lidocaine and prilocaine, Lutrol((R)) F68 and Lutrol((R)) F127, suitable for anesthetizing the periodontal pocket has previously been developed. This consists of discrete micelles with a diameter of 20-30 nm and has a suitable gelation temperature, a good release profile and excellent long-term stability. In this study, the unimer/micelle transition and gel formation of the formulation, in its concentrated state, are investigated using differential scanning calorimetry (DSC), dye solubilization, rheology, and nuclear magnetic resonance (NMR) self-diffusion. The critical micellization temperature (cmt) and gelation temperature are found to be interconnected and influenced by cosolutes, such as electrolytes and hydrophobic substances, the latter as found particularly for the eutectic mixture of the local anesthetic agents lidocaine and prilocaine. Both cmt and the gelation temperature decrease with increasing pH of the system, i.e. at reduced solubility of the active ingredients. Moreover, both cmt and the gelation temperature increase upon diluting the system with water. The ratio between the two block copolymers present in the system also has an impact on both cmt and the gelation temperature, resulting in a decrease in onset temperature of both processes with an increase of Lutrol((R)) F127. The amount of the active ingredients present in the micelle phase depends on the pH of the system being approximately 0% w/w at pH 5, 50-60% w/w at pH 7.8 and 80% w/w at pH 9.
Scherlund
M
M
AstraZeneca R&D, SE-151 85, Sodertalje, Sweden. marie.scherlund@astrazeneca.com
Brodin
A
A
Malmsten
M
M
D000779:Anesthetics, Local / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning / Q000379:methods; D002626:Chemistry, Pharmaceutical; D005782:Gels; D006863:Hydrogen-Ion Concentration; D008012:Lidocaine / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D011108:Polymers / Q000737:chemistry*; D011318:Prilocaine / Q000737:chemistry*; D012995:Solubility
D000779:Anesthetics, Local; D005782:Gels; D008823:Micelles; D011108:Polymers; D011318:Prilocaine; D008012:Lidocaine