Enhancement of Transdermal Delivery By Superfluous Thermodynamic Potential. Iii.1-2) Percutaneous Absorption of Nifedipine in Rats

Abstract

The bioavailability of percutaneous nifedipine was studied in rats. To improve the transdermal delivery of nifedipine, concentration changes due to loss of a volatile component in the vehicle were utilized. The percutaneous absorption of nifedipine was enhanced from binary solvent systems of acetone and propylene glycol (PG) or isopropyl myristate (IPM), compared with the results from simple PG or IPM saturated with the drug. In contrast, no appreciable increases in the percutaneous absorption of nifedipine from PG or IPM above controls were observed for pretreatment of the dosing site with acetone. From a ternary vehicle of volatile/nonvolatile-hydrophile/nonvolatile-lipophile solvent system, i.e., acetone-PG-IPM, a very dramatic enhancement in the bioavailability of nifedipine was noted. In addition, a marked increase in the penetration of PG from the ternary solvent system was found, compared with the result from the binary solvent system of acetone and PG. Nifedipine solutions with the volatile component eventually caused precipitaion at the dosing site and so reduced the plasma nifedipine concentration. The precipitation was inhibited or retarded when polymer additives were incorporated in the ternary solvent system, and the high plasma nifedipine concentrations were maintained. This effect was not diminished when the formulation was administered immediately after the evaporation of acetone. The area under the plasma nifedipine concentration-time curve from the ternary solvent system with a polymer additive was higher by about 75 times than that from PG saturated with the drug. From these observations, we conclude that the increase in the transdermal delivery of nifedipine was caused by the increase in the thermodynamic activity of the drug in the nonvolatile vehicle following the evaporation of the volatile component. © 1987, The Pharmaceutical Society of Japan. All rights reserved.