IONTOPHORESIS OF FLUVASTATIN SODIUM: STUDY OF VARIOUS FACTOR AND IN-VITRO PERMEATION

Fluvastatin sodium (FVS) is the first fully synthetic 3-hydroxy-3-methylglutaryl coenzyme (HMG-CoA) reductase inhibitors used for the treatment of hypercholesterolemia. It shows extensive first pass metabolism with short plasma half-life (3 hrs). The iontophoresis approach was used to determine the permeability of drug through isolated rat skin. In-vitro permeation of drug was determined by using glickfeld diffusion cell. Cathodal iontophoretic delivery was studied and optimized by evaluating donor compartment for the effect of pH, NaCl concentration, current density, pulsed depolarized DC current and drug concentration. Effectual permeation of FVS was obtained in phosphate buffer pH 5. Different concentration of NaCl showed negative effect on the iontophoretic permeation of drug. At higher current density, the rate of permeation was increased. Pulsed depolarized DC current showed higher flux (34.34 µg/cm²/hr) compared to the continuous DC current (26.44 µg/cm²/hr). With increasing concentration of drug, permeation was increased linearly. Comparison between human cadaver skin and rat skin showed that the permeation of drug was decreased from human cadaver skin (443.311±3.53 µg/cm²) as compare to the isolated rat skin (483.841±4.68 µg/cm²) but not showed statistically significant difference. Iontophoretic system containing 3mg/ml concentration of FVS with the area of 3.49cm² would be able to maintain input rate of drug for the period of 12 hrs.