Search

Hydrophilic ionic drugs can be rendered lipophilic by ion-pair formation with hydrophobic counter-ions. This study examines the value of forming ion pairs between anionic salicylate and a series of amines as model cationic counter-ions to facilitate topical delivery and skin penetration. The in-vitro translocation of salicylate ions from a nonaqueous vehicle through human epidermis was estimated in the presence or absence of amines. The distribution into, and accumulation of the salicylate ion in various tissues following topical application to anaesthetised rats were also investigated. Although the epidermal permeation constants of the salicylate-amine ion pairs were lower than that of salicylate itself (enhancement ratios: 0.74-0.87), salicylate retention and localisation in the underlying rat tissues increased in the presence of some of the counter-ions studied. Salicylate concentrations (microg (g tissue)(-1)) in the dermis were 877.2+/-78.6 for salicylate alone and 1098+/-121.9-2586+/-332.5 for salicylate-amine ion pairs. The levels of salicylate in tissues up to the top muscle layer were 1.2-3.7-fold higher in the presence of the counter-ions. It is concluded that, although amine counter-ions have the ability to influence the penetration of salicylate, in-vitro permeability studies do not reflect the in-vivo increases in tissue concentrations resulting from probable changes in systemic clearance.

A slow-release zinc complex, zinc monoglycerolate (ZMG) was examined for its potential gastroprotective activity in various gastric ulcer models. These models comprised (a) oral or parenteral non-steroidal anti-inflammatory drugs (NSAIDs) given to rats whose gastrointestinal mucosa was pre-sensitized by prior development of arthritis, oleyl alcohol-induced inflammation and cold exposure, (b) oral ethanol (12.5-100%) with and without added 4% HCl, (c) intraperitoneal reserpine (5 mg kg-1) in arthritic and normal rats and in normal mice, (d) oral NSAIDs given to mice in which acid and pepsin production was stimulated by co-administration of intraperitoneal bethanechol chloride (5 mg kg-1) to enhance ulcer development, and (e) NSAIDs given to carrageenan-inflamed rats to determine effects of ZMG on paw inflammation. In these models, ZMG given orally was effective in preventing development of gastric lesions, except with propionic acid NSAIDs; the effective doses being apparently dependent on the severity of the mucosal injury. In many of the models ZMG was superior to zinc sulphate and other zinc salts or metal ion complexes investigated but was slightly more effective or equipotent compared with zinc acexamate. ZMG did not impair the anti-oedemic effects of NSAIDs. ZMG is thus an effective agent in preventing ulcer development in a wide range of model systems and may be more effective than zinc salts because of the controlled slow-release of zinc from the complex.