pH effect on the percutaneous penetration of lignocaine hydrochloride

(1) The percutaneous penetration of lignocaine hydrochloride is affected in vitro by the pH; alkalinity increased the portion of the unionized drug which permeated through the lipoid outer skin membrane of guinea pigs. (2) The amount of lignocaine accumulated on the dermal side of the diffusion cell containing isotonic phosphate buffer (pH 7.4) was directly proportional to the initial concentration of the applied drug at the alkaline pH. (3) The dermal transfer rates of lignocaine into the isotonic phosphate buffer (pH 7.4) of the diffusion cell decreased with the increase in the pH of the initially applied solution on the epidermal side of the diffusion cell; the simultaneous cutaneous penetration of the alkaline buffer promoted retention of the unionized drug in the dermis. (4) Percutaneous penetration of lignocaine hydrochloride represents a dual-stage process involving dissimilar rates of clearance into cutaneous tissue and transfer from dermis to body fluids. Variations in the alkaline pH of lignocaine hydrochloride solution appear to govern the rate-limiting factor of the total percutaneous penetration; the pharmacologic action of lignocaine may thus be localized.