Studies on the Absorption of practically Water-insoluble Drugs following Injection. III. Intramuscular Absorption from Aqueous Nonionic Surfactant Solutions in Rats

Abstract

The intramuscular absorption characteristics and kinetics of practically water-insoluble drugs, which were solubilized in water with nonionic surfactants, were studied by the local clearance method in the m. gastrocnemius of the intact rat. The solubilized drugs were absorbed approximately according to 1st order kinetics. Their absorption rates were controlled by the distribution coefficient (K, micellar phase/water phase) as well as the injection volume (V0) and the surfactant concentration (Cs0), but depended little on the vehicle viscosity under the present experimental conditions. A model, based on the assumptions that the drug is distributed instantaneously between the micellar and water phases in the depot and that the drug molecules in both phases are transported into the vascular systems by diffusion at different rates, was proposed to account for the kinetic features of the process. It predicted that the plot of the 1st order absorption rate constant (k) against 1/Cso or 1/K would be approximately linear when the injection volume was fixed, the surfactant absorption was very slow, and the contribution of the drug entrapped in micelles to the absorption was much smaller than that of the free drug. The experimental results agreed well with these predictions, except for the systems of very high surfactant concentration. Experimentally, k was inversely proportional to V01/3 and this was explained reasonably by the model. © 1981, The Pharmaceutical Society of Japan. All rights reserved.