Studies on the Absorption of practically Water-insoluble Drugs following Injection. I. Intramuscular Absorption from Water-immiscible Oil Solutions in Rats

Abstract

The absorption behavior following intramuscular injection of practically water-insoluble drugs in water-immiscible oil solution was investigated with several azo dyes and two steroids as model drugs by the local clearance method in the m. gastrocnemius of the rat. The absorption of the drug component obeyed approximately 1st order kinetics, while the absorption of the oily solvent was very slow. The injection volume (V0) influenced the absorption rate constant (k) and the correlation k ∝ V0m was experimentally observed (for intact rats, m=− 0.14; for anesthetized rats, m=−0.32). This was also the case at another injection site, the m. rectus femoris in rats. Comparison of the absorption rate of a drug in various oil vehicles showed that k was controlled predominantly by the oil/water distribution coefficient (K) and depended little on the viscosity of the vehicle. These results suggested that the release process of the drug component from the oily depot to the aqueous phase around it was the main route for absorption, and that the subsequent transport process in the aqueous phase might be rate-limiting. A plot of log k versus log K gave a straight line with a slope close to -1, but of a slightly smaller absolute value. This plot could be applied satisfactorily for estimating the absorption rate of other drug-oil systems. A guideline for predicting the absorption rate of a drug in oily suspension from the k value for its solution is presented. © 1981, The Pharmaceutical Society of Japan. All rights reserved.