TRANSDERMAL DELIVERY OF BETA BLOCKING DRUGS--IN VITRO AND IN VIVO PERMEATION STUDIES IN THE HAIRLESS MOUSE

Propranolol, atenolol and pindolol, three beta blocking drugs, which vary in their lipid solubility were selected for the study. The Valia-Chien skin permeation system and hairless mouse skin were used for all in vitro studies.;Semisolid formulations of all three drugs were made and three formulations were selected for further studies. A newly developed silicone based emulsion formulation showed a remarkable improved permeability with all three drugs. Pindolol was permeable to a higher extent than atenolol or propranolol from this formulation. The permeability coefficient of propranolol was 1.5 times lower than that obtained for atenolol from this formulation. The possible reason for such a reversal compared to permeability coefficients determined in aqueous media, is discussed based on formulation factors.;Two other formulations, a polyethylene glycol (PEG) base and a gel base were also investigated. Both propranolol and atenolol showed very low permeability from these two formulations. Pindolol permeability from the PEG base was however similar to that obtained from the emulsion formulation.;In vivo studies in hairless mice using the emulsion formulation containing propranolol were carried out. A method for transdermal administration and blood sampling in this species was developed and may be used for screening transdermal formulations, devices and drugs with potential for transdermal delivery. A fluorometric method for the plasma level determination of the drug was also developed.;Flux versus donor solution concentrations for propranolol showed a linear relationship. The permeability coefficient of propranolol, a highly lipid soluble drug, was four times that of atenolol, a highly water soluble drug. The permeability coefficient of pindolol, a semipolar drug was higher than that of propranolol or atenolol indicating that the requirement of a balance in lipid solubility for transdermal delivery may be an important consideration.;Plasma levels of greater than 200ng/ml were achieved from the formulation. Removal of the transdermal patch caused plasma levels to fall below detectable limits by eight hours. The formulation developed is believed to have potential for use as a drug reservoir in transdermal delivery devices. General insight into the process of transdermal delivery and formulation factors affecting transdermal delivery based on the results of the experiments are discussed.