Stabilization of supersaturated solutions of a lipophilic drug for dermal delivery

The stability of supersaturated solutions of a model lipophilic drug (LA-P, a lavendustin derivative) in propylene glycol-water mixtures prepared usin g the method of mixed cosolvents was investigated. The solutions had a fixe d degree of saturation (DS = 4), but contained different ratios of propylen e glycol-water. The absolute concentrations of LAP in these solutions varie d by approximately a factor of 40, but the solutions at lower concentration s 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 t he absolute drug concentration. Solutions of up to 5 degrees of saturation in 7:3 propylene glycol-water mixture were stable when stored for several h ours; those at higher degrees of saturation recrystallized immediately. Whe n the solutions were stirred, recrystallization occurred more rapidly. The influence of various polymeric additives on the stability of the supersatur ated solutions showed that only sodium carboxymethyl cellulose had a stabil izing effect; however, the solution was very viscous and it is not clear wh ether the stabilizing effect was due to this high viscosity or to a specifi c interaction between drug and polymer. (C) 2001 Elsevier Science B.V. All rights reserved.