N. dibutyl Succinate as a Solvent for Parenteral Injection

Abstract

Recently we have had occasion to test the toxicity of some water insoluble drugs. Lipschitz et al. 1 after extensive studies with various organic esters stated that N. dibutyl succinate showed a minimal toxicity when injected intramuscularly into rats and believed the agent suitable as a solvent for parenteral injections. This agent was selected for the solvent of our drug and was injected intra peritoneally into rats.∗ Using constant amounts of the solvent with varying amounts of the drug to be tested, it was observed that all the rats behaved in a very peculiar manner, regardless of drug dosage. The solvent alone was tried by intraperitoneal injection and it was found that the solvent accounted for all the reactions observed.

A series of 20 albino rats weighing from 200 to 250 g were injected with the N. dibutyl succinate in graded amounts from 0.5 cc to 10 cc per kg intraperitoneally. The first effect observed was a tendency to gnaw the hind toes, then the rats assumed a somewhat flat crawling position, tending to drag the hind limbs. In a few minutes all the rats became sedated, and dropped off to sleep, with sudden rousing, dragging themselves about the cage and relapsing again into sleep. Respiration was quite markedly decreased. The minimal doses produced this effect lasting about one hour while the effects persisted for nearly 3 hours with the larger doses. All the animals recovered.

In view of the desirability of checking these observations with material from a different source, we obtained a second sample of the solvent from the Eastman Kodak Company. Twenty albino rats of about 200 to 250 g were selected and 10 were injected with the Eastman product and 10 with the original sample in doses of 0.5 cc to 5 cc per kg intraperitoneally.