Nanostructured lipid carriers as robust systems for topical lidocaine-prilocaine release in dentistry

In dental practice, local anesthesia causes pain, fear, and stress, and is frequently the reason that patients abandon treatment. Topical anesthetics are applied in order to minimize the discomfort caused by needle insertion and injection, and to reduce the symptoms of superficial trauma at the oral mucosa, but there are still no efficient commercially available formulations. Factorial design is a multivariate data analysis procedure that can be used to optimize the manufacturing processes of lipid nanocarriers, providing valuable information and minimizing development time. This work describes the use of factorial design to optimize a process for the preparation of nanostructured lipid carriers (NLC) based on cetyl palmitate and capric/caprylic triglycerides as structural lipids and Pluronic 68 as the colloidal stabilizer, for delivery of the local anesthetics lidocaine and prilocaine (both at 2.5%). The factors selected were the excipient concentrations, and three different responses were followed: particle size, polydispersity index and zeta potential. The encapsulation efficiency of the most effective formulations (NLC 2, 4, and 6) was evaluated by the ultrafiltration/centrifugation method. The formulations that showed the highest levels of encapsulation were tested using in vitro release kinetics experiments with Franz diffusion cells. The NLC6 formulation exhibited the best sustained release profile, with 59% LDC and 66% PLC released after 20 h. This formulation was then characterized using different techniques (IR-ATR, DSC, DRX, TEM, and NTA) to obtain information about its molecular organization and its physicochemical stability, followed during 14 months of storage at 25 °C. This thorough pre-formulation study represents an important advance towards the development of an efficient pre-anesthetic for use in dentistry.

Schematic representation of the individual NLC/LDC-PLC considers the estimated number of molecules of each excipient in a nanoparticle. P68 = Pluronic 68, LDC-PLC = the eutectic mixture of lidocaine and prilocaine, SL = solid lipid, and LL = liquid lipid.208