Influence of drug lipophilicity on drug release from sclera after iontophoretic delivery of mixed micellar carrier system to human sclera

Abstract

Mixed micelles prepared using sodium taurocholate (TA) and egg lecithin (LE) were previously found to be an effective carrier for sustained release of a poorly water-soluble drug in transscleral iontophoretic delivery. The objectives of the present study were to investigate the effects of drug lipophilicity upon micellar carrier solubilization potential and drug release profiles from the sclera after iontophoretic delivery of model lipophilic drugs dexamethasone (DEX), triamcinolone acetonide (TRIAM), and β-estradiol (E2β) with a mixed micellar carrier system of TA-LE (1:1 mole ratio). In this study, the micellar carrier system was characterized for drug solubilization. The micelles encapsulating these drugs were evaluated for transscleral passive and 2-mA iontophoretic delivery (both cathodal and anodal) and drug release from excised human sclera in vitro. The results show that drug solubility enhancement of the micellar carrier system increased with increasing drug lipophilicity. The more lipophilic drugs E2β and TRIAM displayed slower drug release from the sclera compared with the less lipophilic drug DEX after iontophoretic drug delivery with the mixed micelles. These results suggest that the combination of transscleral iontophoresis and micellar carriers is more effective in sustaining transscleral delivery of the more lipophilic drugs studied in this investigation.

Figure 1

Drug solubilization enhancement (ratios of solubilities of DEX, TRIAM, and E2β in the mixed micellar carrier systems to controls) versus drug log K_o/w.

Figure 2

Cumulative amount of (a) DEX, (b) TRIAM, and (c) E2β released from human sclera versus time in the release study performed after passive (closed diamonds), cathodal iontophoresis (closed squares), and anodal iontophoresis (closed triangles) of mixed micelles and passive (open diamonds), cathodal iontophoresis (open squares), and anodal iontophoresis (open triangles) of the controls. Data represent the mean and standard deviation, n ≥ 3.

Figure 3

(a) Percentage of DEX, TRIAM, and E2β released from sclera at time point 48 h versus drug log K_o/w in the drug release study and (b) loading enhancement of the drugs into the sclera by the mixed micelles compared with the controls versus drug log K_o/w after passive transport (diamonds), cathodal iontophoresis (squares), and anodal iontophoresis (triangles). Data represent the mean and standard deviation, n ≥ 3.