The penetration of supersaturated solutions of piroxicam across silicone membranes and human skin in vitro

Under ideal circumstances, maximum flux is achieved from saturated solutions and, therefore, the diffusion of compounds from supersaturated solutions would provide enhanced penetration. However, due to the inherent lack of stability of supersaturated solutions, they tend to crystallise upon preparation, but in some cases this can be overcome with antinucleant polymers which inhibit or retard crystallisation. Supersaturated solutions of piroxicam for a range of different degrees of saturation up to 5.3 were prepared in a 40:60, v/v, propylene glycol/water cosolvent mixture. Solutions up to 4 degrees of saturation were stable for at least 16 h and their penetration across silicone membranes and full-thickness human skin was investigated using diffusion cells. Relationships between flux and degree of saturation for the supersaturated systems produced linear correlations, but flux values across skin at 0.5 and 1 degrees of saturation were similar. This was partly attributed to differences in the solubility of the drug at different donor phase temperatures. Mechanisms of action for antinucleant polymers were considered, and it was postulated that hydroxypropylmethyl cellulose prevented the formation of a hydrate form of piroxicam, which was less soluble than its anhydrous form in aqueous based solvent systems.