Stabilization of supersaturated solutions of a lipophilic drug for dermal delivery

The stability of supersaturated solutions of a model lipophilic drug (LAP, a lavendustin derivative) in propylene glycol-water mixtures prepared using the method of mixed cosolvents was investigated. The solutions had a fixed degree of saturation (DS=4), but contained different ratios of propylene glycol-water. The absolute concentrations of LAP in these solutions varied by approximately a factor of 40, but the solutions at lower concentrations were no more stable than the more concentrated solutions. This shows that stability is primarily a question of the degree of saturation and not of the absolute drug concentration. Solutions of up to 5 degrees of saturation in 7:3 propylene glycol-water mixture were stable when stored for several hours; those at higher degrees of saturation recrystallized immediately. When the solutions were stirred, recrystallization occurred more rapidly. The influence of various polymeric additives on the stability of the supersaturated solutions showed that only sodium carboxymethyl cellulose had a stabilizing effect; however, the solution was very viscous and it is not clear whether the stabilizing effect was due to this high viscosity or to a specific interaction between drug and polymer.