Abstract
The influence of additives in topical formulation (cataplasm) on delivering piroxicam (Px) to local tissue underlying the application site was investigated. The additives were chosen from the group of fatty acids, their esters, carbohydrates, cyclic alcohols or polyhydric alcohols. In vivo experiments were carried out using guinea-pigs. Also, the solubility of Px in those additives was determined and compared with the plasma concentration at 8 hours after application of cataplasm containing corresponding additives. Those cataplasms containing high Px solubility additives showed relatively high plasma concentration, whereas those containing relatively low Px solubility resulted in lower plasma concentration. The inorganic/organic ratio of additives which showed the higher plasma concentration as well as the higher Px solubility was located in between 0.5 and 2.0 in organic conceptual diagram. The Px concentration in plasma and in muscle beneath the application was measured with the formulation containing 20% of propylene glycol (PG) and additives. Diisopropyl adipate (DIA), diethyl sebacate and triacetin showed relatively high plasma concentration at 8 hours after application. The ratio of muscle/plasma concentration by DIA was found to be the highest among them. The influences of the amount of DIA and PG on Px in plasma, viable skin, cutaneous muscle and muscle were investigated. DIA and PG increased the Px delivery to the local tissues with concentration dependent manner.
