Pharmacokinetics of triamcinolone acetonide in rabbit skin following iontophoretic administration

Several researches show that the main challenge in transdermal drug delivery is to overcome the inherent barrier of the skin. The rate limiting step in transdermal transport occurs at the stratum corneum level, the outermost layer of the skin, which plays an important role as a port of entry of therapeutic agents into the body for the systemic as well as topical actions. Iontophoresis is a non-invasive technique for transporting charged molecules into and through tissues by a mild electric field. In addition to the enhanced continuous transport, iontophoresis allows dose titration by adjusting the electric field, which makes personalized dosing feasible.;Microdialysis is an excellent and powerful semi-invasive method working on the principle of dialysis which gives protein free samples. It is also a good alternative to measure unbound drug concentrations in the body which actually reflects the bioavailability of the drug. The loss of drug from the perfusate is referred to as retrodialysis. The principle of this method relies on the assumption that the diffusion process is quantitatively equal in both directions through the semi permeable membrane.;Triamcinolone Acetonide has been used to treat inflammatory and proliferative ocular disorders, such as uveitis, cystoids macular edema, proliferative vitreoretinopathy and choroidal neovascular membrane secondary to age related macular degeneration. It is also been used in keloids. The purpose of this study is to investigate the feasibility and mechanisms of iontophoretic delivery of Triamcinolone Acetonide to rabbit dermis.;A simple and selective high performance liquid chromatographic method is been used far the determination of TA dialysate samples using Symmetry RTM C18 5mum 4.6x150 min column; the mobile phase for the separation of TA consists of a mixture of acetonitrile and water (40:60 v/v). The analysis time was less than 8 min, at a flow rate of 1 mL/min and detection at 254 nm. The lower limit of quantification (LLOQ) for dialysate samples was found to be 25 ng/mL and for plasma samples, it was 50 ng/mL. The average plasma extraction efficiency was 92.8 +/- 1.5%.;In vitro microdialysis studies of TA recovery and extraction were conducted at 37°C to validate the method before in vivo studies. In vitro extraction and retrodialysis were identical, 54.93 +/- 4.71 (n=14) and 56.48 +/- 3.87 (n=14) respectively. Linear microdialysis probes had a 10 mm window made of polyacrylonitrile hollows fibres with a 50 KDa molecular weight cut off.;In vivo retrodialysis recovery was found to be 48.01 +/- 4.11%. For the in vivo iontophoretic study, we used two different kinds of market available patches. They were steel based patch and IOMED patch. They both were studied with variable current densities and variable sample collection interval but neither of them gave satisfactory results. Also we performed a total of 4 experiments with market available TA formulations i.e. the cream, lotion, ointment but they all gave no remarkable results than expected. In conclusion, no TA was detected in dermis by microdialysis sampling following either iontophoresis or passive delivery from commercial products. One of the reasons for this may be that the drug might not be available in the ECF in the free form. Other highly sensitive methods like biopsy, skin stripping etc can give good results rather than the method that we used for our experiments.