Studies on the absorption of practically water-insoluble drugs following injection. IV. An approach for predicting relative intramuscular absorption rates of a drug in oily solution, aqueous suspension and aqueous surfactant solution in rats

This investigation was undertaken to evaluate the differences of intramuscular absorption rates of practically water-insoluble drugs in rats among the three basic dosage forms : oily solutions (including oily suspensions), aqueous suspensions, and aqueous solutions containing nonionic surfactants as solubilizers. A review of previous studies indicated that the rank order of magnitude of the absorption rates among such dosage forms was not fixed, but varied remarkably depending on the drug, the oily solvent, the surfactant and its concentration, and colloidal properties such as particle size, etc., in addition to the initial drug concentration and injection volume. Thus, we sought to establish a method for predicting the relative absorption rates from the three dosage forms empirically. The feasibility of the proposed approach was confirmed experimentally with testosterone for the three dosage forms injected intramuscularly into intact rats. In conclusion, this approach is expected to provide a novel and useful guide not only for predicting the relative absorption rates from various dosage forms but also for selecting optimal preparations for more detailed screening and preclinical testing in laboratory animals of new drugs under development.