In vitro percutaneous permeability enhancement of nimodipine by limonene across the excised rat abdominal skin.

The purpose of the present study was to investigate the effect of limonene on the in vitro permeation of nimodipine across the excised rat abdominal skin from a 2% w/w hydroxypropyl methylcellulose (HPMC) gel drug reservoir system. The HPMC gel formulations containing 1.5% w/w of nimodipine and selected concentrations of limonene (0% w/w to 8% w/w) were prepared, and subjected to in vitro permeation of the drug through excised rat abdominal epidermis. The drug content in the gels was found to be uniform, and the drug was found to be stable in HPMC gel formulations. The flux of nimodipine across rat epidermis was markedly increased by the addition of limonene to the HPMC gels. A maximum flux of nimodipine was observed (203+/-0.6 microg/cm2 x h) with an enhancement ratio of about 5.7 when limonene was incorporated in HPMC gel at a concentration of 4% w/w. However, there was no further increase in the permeability of nimodipine beyond 4% w/w of limonene in the HPMC gel. FT-IR data indicated that limonene increased the permeability of nimodipine across the rat epidermis by partial extraction of lipids in the stratum corneum. The results suggest that limonene is useful for enhancing the skin permeability of nimodipine from transdermal therapeutic systems containing HPMC gel as a reservoir.