Optimisation of Cosolvent Concentration for Topical Drug Delivery – II: Influence of Propylene Glycol on Ibuprofen Permeation

Abstract

The influence of formulation components on drug thermodynamic activity and on membrane properties has not been extensively studied to date. Propylene glycol (PG) has a long history of use as a component of topical pharmaceutical and cosmetic preparations. In the present study we investigated the influence of PG on the solubility and membrane permeability characteristics of ibuprofen in silicone and skin using binary (PG:water) and ternary (ethanol:PG:water) solvent systems. Fluxes were maximum for 70:30 PG:water systems in silicone membrane; however, for experiments conducted with skin, the flux of ibuprofen systematically increased with increasing amounts of PG. For silicone membrane, the flux values of ibuprofen from ternary ethanol:PG:water (25:25:50 and 50:25:25) systems were 1.2- and 1.5-fold higher than the highest values observed from the PG:water systems. A comparison of the data from occluded versus non-occluded studies suggested that the ethanol content was the critical determinant of flux enhancement in these systems. For human skin, a PG:water (50:50) mixture enhanced ibuprofen flux to the same extent as the corresponding ethanol:PG:water (25:25:50) system. However, the ternary system, ethanol:PG:water (50:25:25), demonstrated the greatest enhancement. An analysis of the partition and diffusion parameters for experiments conducted with skin confirmed that the influence of PG in the PG:water systems is primarily on the solubility and partitioning behaviour of ibuprofen. The ternary systems also appear to influence skin partition behaviour rather than diffusivity when compared with the permeation parameters of ibuprofen from saturated aqueous solutions.