Category: Formulation and Quality
Purpose: The diffusion testing of topical formulations has long been examined using vertical (Franz type) diffusion cells. This requires the use of relatively large volumes of sample and lacks the air/membrane interface representing the in vivo skin condition for some pharmaceutical formulations and applications. Previously we have demonstrated the in vitro permeability of diclofenac sodium is dependent upon the method of application in diffusion studies. Here we examine the permeability of lidocaine hydrochloride formulations using Franz chambers and our air interface chamber the Munt/Dash diffusion chamber (Figure 1).
Methods: Lidocaine was quantified using an UPLC method with a photodiode array (210 nm) detector. Shed snake skin was dried, flattened, and cut to fit the diffusion chambers. Prior to experimentation snake skin was equilibrated overnight in DPBS. To prevent leakage skins were clamped between Teflon foam gaskets on both Franz and Munt/Dash chambers. Permeability studies were carried out on 3 different formulations at room temperature and 32°C over a period of 5 hours. All the data represents the mean and standard error from six samples.
Results: At room temperature, a commercial topical lidocaine formulation showed a steady state flux of 0.069 ± 0.003 μMol/cm2*hour using a Franz chamber and 0.006 ± 0.002 μMol/cm2*hour using the Munt/Dash diffusion chamber. However, at 32°C steady state fluxes were 0.113 ± 0.04 μMol/cm2*hour and 0.009 ± 0.003 μMol/cm2*hour as measured using Franz and Munt/Dash diffusion chambers, respectively (Figure 2). Other aqueous formulations showed similar trends in lidocaine flux through shed snake skin.
Conclusion: Lidocaine is known to have poor transdermal permeability in the absence of penetration enhancers (0.00003 μMol/cm2*hour by in vivo microdialysis, Xie et al., 2016). However, previous reported in vitro Franz studies using lidocaine formulations by Kushla et al., 1989, showed a flux of approximately 0.11 -0.29 μMol/cm2*hour through human stratum corneum. This in vitro data agrees well with our Franz data. However, even our air interface data shows a much greater flux than the previously reported in vivo data. This higher flux may be attributed to the differences between human stratum corneum and shed snake skin as well as the presence of penetration enhancers in the formulations. With high inter-patient and inter-formulation variability, the major conclusion of these studies is that Franz chambers and Munt/Dash chambers do produce significantly (P< 0.01) different flux data. Further paired in vitro and in vivo studies are needed to examine the use of both diffusion chambers for IVIC.
Xie F, Chai J, et al. Transdermal permeation of drugs with differing lipophilicity: Effect of penetration enhancer camphor. Int J Pharm. 2016 Jun 30;507(1-2):90-101.
Kushla Gp, Zatz, JL. Lidocaine penetration through human and hairless mouse skin in vitro. J Soc Cos Chem. 1989;40:41-50.