Influence of propylene glycol as cosolvent on mechanisms of drug transport from hydrogels

Abstract

The in vitro penetration of topical glucocorticoids (GC) betamethasone 17-valerate (BMV), hydrocortisone 17-butyrate (HCB) and hydrocortisone (HC) into an artificial lipid acceptor and excised human skin was examined using binary hydrogels with varying propylene glycol (PG) content. The relationship between the physicochemical properties of the model drugs in binary PG/water mixtures and the rate and extent of their penetration into artificial lipid membranes was studied. As a function of the drug solubility and partition behavior between lipid acceptor and PG/water mixtures, two directions were found in which PG affects the penetration of the GCs used. The lipophilic BMV, providing a higher solubility in the acceptor lipid than in PG/water mixtures of the formulations, penetrates thermodynamically controlled. In this case, PG acts only as cosolvent. For the more hydrophilic HC with higher solubilities in PG/water mixtures than in the acceptor medium, the amount penetrated increases with increasing PG content of the formulation. This result is surprising because of the expectation that the rate and extent of penetration decrease with decreasing partition coefficients. PG penetrates rapidly into the artificial acceptor and into excised human skin. It acts as both cosolvent and enhancer. In the case of HC transport, the enhancer effect is supposed to be a solvent drag effect of PG. HCB seems to penetrate thermodynamically controlled up to 40% PG. However, if PG contents of 60 and 80% are used in the gels the drag transport mechanism dominates. The results obtained from the studies with the lipophilic acceptor membranes were confirmed using excised human skin.