Correlation between in vitro permeation and in vivo anesthetic efficacy

Objectives: To correlate the in vitro permeation with the in vivo topical efficacy of lidocaine- containing formulations evaluated previously (needle insertion/anesthetic injection) in order to predict the effectiveness of new designed topical anesthetics. Methods: Permeation (flux and permeability coefficient - P) of lidocaine across pig-palatal mucosa was studied using the Franz-type diffusion cells. Liposome-encapsulated 5% lidocaine (LipoLido5%), Liposome-encapsulated 2.5% lidocaine (LipoLido2.5%), Eutectic Mixture of Lidocaine/Prilocaine 5% (EMLA^®) and 5% lidocaine (Xylocaína^®) were applied non-occlusive in infinite dose conditions in the donor compartment. Samples were periodically withdrawn from the receptor phase and analyzed by HPLC. Results: Table 1 shows mean and 95%IC of permeation parameters of lidocaine across pig palatal mucosa (Figure 1) and the in vivo parameters (Visual Analogue Scales-VAS).

	Flux (mg.cm-2.h-1)		P (cm.h-1).103		VAS-Insertion (cm)		VAS-Injection (cm)
	mean	95%CI	mean	95%CI	mean	95%CI	Mean	95%CI
EMLA®	0.236	7.19 - 11.7	9.44	7.2 - 11.7	1.15	0.68 - 1.62	1.3	0.82 - 1.78
Xylocaína®	0.087	0.46 - 2.99	1.73	0.46 - 2.99	2.16	1.59 - 2.73	2.47	1.76 - 3.18
LipoLido2.5%	0.163	4.85 - 8.16	6.51	4.85 - 8.16	1.83	1.32 - 2.34	2.26	1.66 - 2.85
LipoLido5%	0.440	8.02 - 9.59	8.80	8.02 - 9.59	1.68	1.08 - 2.29	1.78	1.17 - 2.39

Results: LipoLido5% and Xylocaína^® showed, respectively highest and lowest flux when compared to the other formulations (ANOVA, p<0.05). No statistically significant differences (ANOVA, p>0.05) were observed between EMLA and LipoLido5% regarding P, and both showed higher P than the other formulations. A high (rPearson>0.7, p>0.05) correlation was verified between P and VAS-Injection. There was moderate (rPearson>0.3, p>0.05) correlation between flux and VAS-Insertion; and P and VAS-Insertion. Conclusion: There is a correlation between in vitro and in vivo parameters. In vitro studies could be helpful to predict the effect of topical anesthetic agents.