Absorption of drugs from the skeletal muscle of the rats. 3. Effect of water-soluble adjuvants and vehicles on the intramuscular absorption.

The effect of various kinds of adjuvants or vehicles was studied with a view to examine the mechanism of intramuscular drug absorption. From the relationship between in vitro absorption studies and various in vitro diffusion experiments, it was clarified which step was the rate-limiting one in the intramuscular absorption.1) The absorption mechanism of a drug with water-soluble adjuvants did not differ from that in aqueous solution without any adjuvant.2) There was a good correlationship between the parenteral absorption rate and the reciprocal of viscosity of an injectable solution, provided that the molecular weight of an adjuvant was comparatively small such as propylene glycol, glycerin, and PEG 400. Effect of these solvents on the drug absorption was general in nature and not specific to drugs. In the case of an adjuvant having higher molecular weight such as PEG 4000 dextran, and methylcellurose, rate of drug absorption was greater than that expected from the viscosity, suggesting that macromolecules could hardly diffuse through the pores of the capillary wall.3) From in vitro diffusion study using Visking membrane, glass filter, and slice of muscle, it was concluded that the contribution of the diffusion process through the pores of capillary wall was dominant compared with the one through the muscle fiber space.