Mechanism of the inhibitory effect of surfactants on intramuscular absorption of drugs

The mechanism of the absorption inhibitory effect of surfactants on the intramuscular absorption of drugs was investigated. The following observations were demonstrated. 1) All surfactants used in this study whether nonionic or ionic caused solubilization of muscle protein. A good correlation between the solubilization of muscle protein and the absorption inhibitory effect was also found except in the case of the nonionic surfactant HCO-120. 2) The effect of hyaluronidase in the absence or presence of various concentrations of polysorbate 80 on the intramuscular absorption of drugs of different molecular weight was examined. The coexistence of hyaluronidase and polysorbate 80 greatly affected the absorption of drugs. This was depending upon the molecular size of diffused drug and the concentration of surfactant. It was found that increasing the concentrations of polysorbate 80 in the presence of hyaluronidase was accompanied by an inhibition in the absorption of isonicotinamide and abolishment of the accelerating effect of hyaluronidase on the absorption of 14C-sucrose, but it could not show any effect on the absorption of 14C-inulin. 3) The permeability coefficient of gelatin-sodium chondroitin sulfate mixed membrane in the presence of polysorbate 80 was decreased significantly. From these results, it can be concluded that the surfactants interacted with proteins and mucopolysaccharides which are the main components of connective tissue, consequently the intramuscular absorption of drugs was extremely inhibited.