The effect of Miglycol 812 oil on the oral absorption of propranolol in the rat.

This work has examined the effect of Miglyol 812 oil and its composite fatty acids on the oral absorption of propranolol with reference to its intravenous (i.v.) pharmacokinetics. Propranolol hydrochloride, spiked with 4-(3) H labelled compound, was administered i.v. or orally to male Wistar rats and blood concentrations of parent material determined by liquid scintillation counting after extraction into toluene. An i.v. dose-linearity study indicated dose-independent pharmacokinetics for propranolol at 1-2 mg kg-1, with a mean Cls, Vss, MRTi.v. and t0.5 beta of 0.076 L min-1 kg-1, 4.74 L kg-1, 57.81 min and 47.10 min, respectively. At 5 mg kg-1, there was evidence of non-linearity with MRTi.v. increased by about 250%, Vss by 170% and t0.5 beta by 230% compared with the lower doses. After oral administration of propranolol (10 mg kg-1) in aqueous solution, with or without Tween 80 (6%), the mean absorption time (MAT) and terminal half-life were approximately 55 min and 86 min, respectively. The MAT for propranolol administered in a 50% octanoic and lauric acid (1:1 by weight) oil-in-water emulsion, stabilized with 6% Tween 80 (129-90 min), was significantly longer compared with that for a 50% Miglyol 812 oil-in-water emulsion containing the same surfactant (16.55 min). The terminal half-life of propranolol administered in the fatty acid formulation (128.96 min), unlike that for the Miglyol emulsion (54-37 min), was significantly longer compared with that observed after i.v. administration (t0.5 beta = 47 min).(ABSTRACT TRUNCATED AT 250 WORDS)