Diffusive transport properties of some local anesthetics applicable for iontophoretic formulation of the drugs.

As part of a general study to improve the iontophoretic delivery of local anaesthetics of the amide type, the diffusion properties of the hydrochloride salts of bupivacaine, etidocaine, lidocaine, mepivacaine, prilocaine and ropivacaine, were studied in a 1% w/w agarose hydrogel. A source drug solution (25 mM) was placed in contact with the gel and, after an appropriate time, the drug concentration profile in the gel was analyzed to give a diffusion coefficient, D. The values of Dx10(10) expressed in m(2) s(-1) were: (bupi) 6.71, (eti) 6.71, (ropi) 6.39, (mepi) 7.31, (lido) 7.49 and (prilo) 7.76. For comparative reasons, the diffusion coefficient for LidHCl in an aqueous solution according to the Nernst-Hartley relation for the diffusion of ion-pairs was calculated, hereby taking into account ionic activity of LidH+ and Cl-. The diffusion coefficient thus obtained was 7.76x10(-10) m2 s-1 at infinite dilution. The relationship between the molecular weight of the compounds and the diffusion coefficient was investigated.