Desenvolvimento de formulações semi-sólidas contendo anestésicos locais em sistemas nanoparticulados

AUTOR(ES)
DATA DE PUBLICAÇÃO

2009

RESUMO

Objectives: This work aimed to develop and characterize semi-solid formulations containing local anesthetics freely dispersed or entrapped in solid lipid nanoparticles and to evaluate in vivo the analgesic effect of these formulations through tail flick method. Methods: Three semi-solid formulations (gel, cream-gel and silicone emulsion) containing free local anesthetics were developed and modified to achieve similar viscosities. These formulations were characterized in relation to pH, viscosity, drug concentration and stability. Solid lipid nanoparticles (SLN) containing the anesthetics agents were prepared by high pressure homogenization method. These formulations were characterized in relation to pH, drug concentration, entrapment efficiency, particle size, zeta potential and polydispersity index (PDI). Afterwards, they were put into semi-solid formulations. The analgesic effect of all of the formulations was evaluated in vivo in mice tails by means of tail flick method. Formulations without drugs were previously prepared to evaluate the viability of the systems. Results and Discussion: The rheological characteristics of all of the formulations containing 5 % of drugs were similar, showing a non-Newtonian pseudoplastic behavior fitting to Ostwald model. The pH was adjusted to 8.5. The formulations were stable at 40°C during 24 hours when evaluated in TurbiScan LAb®. The SLN suspensions using cetyl palmitate, Lipoid 40®, 5 % of drugs, three homogenization cycles and 500 bar were more adequate considering physicochemical properties (mean particle size=138 nm and PDI=0.17). All formulations presented higher analgesic effect than aqueous solution of drugs and commercial product when evaluated by tail flick method. Gel and cream-gel showed analgesic effect higher than silicone emulsion. SLN suspensions and semi-solid formulation containing these suspensions prolonged the duration of the anesthetic effect in 90 minutes (60 min without SLN to 150 min with SLN) as well as delayed the time-to-peak effect. Conclusion: The formulations developed are stable and showed higher analgesic effect than commercial cream, especially for SLN, whose duration of effect was two times longer than formulations containing free local anesthetics.

ASSUNTO(S)

solid lipid nanoparticles anestésicos locais nanoparticulas high pressure homogenization local anesthetics tail flick method

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