Use of solubility parameters of drug and vehicle to predict flux through skin

The solubilities of theophylline in, and fluxes through skin from, isopropyl myristate, octanol, dimethylformamide, propylene glycol, ethylene glycol, and formamide have been determined experimentally. Values for experimental permeability coefficients (Kp) corresponding to the respective fluxes were determined from, flux/solubility = Kp, which were then compared with values for the respective theoretical partition coefficients (PC) calculated from the known solubility parameters for the vehicles (delta v), theophylline (delta i) and skin (delta s). There was a good correlation for theoretical log PC - 2.52 = experimental log Kp for vehicles exhibiting solubility parameters in the range of delta v = 12-18 (cal/cm3)1/2. This allows relative fluxes to be determined from calculated theoretical partition coefficients and experimentally determined solubilities in that range. For vehicles or mixtures of vehicles exhibiting solubility parameters in the range of delta v = 8-12 (cal/cm3)1/2 large increases in fluxes and permeability coefficients, compared with those predicted from the results in the delta v = 12-18 (cal/cm3)1/2 range, were observed because of vehicle effects on the skin caused by the similarity in solubility parameters of those vehicles to that of skin. Qualitatively, fluxes and permeability coefficients were found to be inversely dependent on drug solubility in the vehicles with a minimum that corresponded approximately to the point where delta i = delta v.