salicylates and oxybutynin

The effects of supersaturated formulations on drug permeation through artificial and biological membranes have been reported by a number of research groups. However, little information is known about solvent permeation from these supersaturated formulations, and in particular the effect of high drug concentrations and degree of saturation (DS) on solvent activity. The aim of this study was to determine the effect of the DS of a model drug, oxybutynin, on solvent and drug permeation. Supersaturated residues of oxybutynin in propylene glycol (PG) or (octyl salicylate) OSAL were prepared by the solvent evaporation method. In both formulations a high percentage (25%, v/v) of solvent was used in order to avoid solvent depletion. Permeation of PG and OSAL through silicone was monitored by GC and HPLC, respectively. All OSAL formulations permeated to a higher extent than PG formulations. A decrease in OSAL permeation with 5 DS formulations was observed in comparison with 1 DS or 2 DS formulations, indicating a decrease in solvent activity with drug concentration. In addition, the drug transport from the 5 DS formulation of OSAL was higher than the 1 and 2 DS formulations but lower than predicted. Based on both solvent and drug permeation, this suggests that the low drug permeation observed with 5 DS resulted from a decrease in solvent thermodynamic activity rather than a decrease in solute activity as a result of drug crystallisation. Using PG formulations, the PG permeation remained unaffected with the DS of the formulation, up to 5 DS.

Topics: Administration, Cutaneous; Chemistry, Pharmaceutical; Drug Delivery Systems; Mandelic Acids; Membranes, Artificial; Permeability; Propylene Glycol; Salicylates; Silicones; Solvents; Thermodynamics