In vivo iontophoretic delivery and pharmacokinetics of salmon calcitonin.

In vivo iontophoretic delivery of salmon calcitonin (SCT) in hairless rats using a self-contained wearable and disposable iontophoretic patch was investigated. Iontophoretic patches with built-in proprietary Zn/AgCl electrodes were used. SCT was formulated in citrate buffer (50mM, pH 4.0) to impart a positive charge for anodal iontophoresis. SCT was delivered intravenously to determine primary pharmacokinetic parameters. Pharmacokinetics of iontophoretic delivery of SCT was compared with subcutaneous route of administration. Blood samples were collected through tail vein and analyzed for serum SCT and calcium levels. Pharmacokinetic parameters were calculated by non-compartmental analysis. An average current of 0.43+/-0.01 mA was maintained during patch application. Iontophoretic patches delivered SCT at an average infusion rate of 177.9+/-58.7 ng/(min kg) and an average steady state concentration of 7.58+/-1.35 ng/ml was achieved. There was no difference between the calcium lowering effect of iontophoretic patch and subcutaneous injection (p>0.05). Clearance and half-life of SCT after IV administration were found to be 16.8+/-0.9 ml/(min kg) and 33.5+/-3.3 min, respectively. The iontophoretic delivery of SCT was well defined by a one-compartment model with zero-order infusion. Iontophoretic patch delivered therapeutically relevant concentrations of SCT in hairless rats and delivery was comparable to conventional routes.

Dermal, subdermal, and systemic concentrations of granisetron by iontophoretic delivery.

PURPOSE: The purpose of this work was to demonstrate the iontophoretic delivery of granisetron hydrochloride by novel, self-contained iontophoretic patches and to determine the subcutaneous and dermal absorption kinetics using microdialysis. METHODS: In vitro iontophoretic delivery of granisetron hydrochloride was evaluated at 5, 10, or 20 mg/ml concentrations of donor using Franz diffusion cells and hairless rat skin as a membrane. In vivo studies were performed in hairless rats. Animals received either subcutaneous or dermal microdialysis probes and iontophoretic patches filled with drug formulation were applied on the abdominal area such that the probe lies below the anode chamber. Blood and microdialysate samples were collected at different time intervals. Intravenous administration of granisetron was also done to determine the basic pharmacokinetic parameters. RESULTS: Iontophoretic patches delivered current constantly throughout the patch application. The patches delivered granisetron hydrochloride at a rate of 14.91+/-4.53 microg/min/kg. Similar concentrations of granisetron hydrochloride in dermal and subcutaneous tissue were observed. Depot formation was identified in the subcutaneous and dermal profiles, indicating that subcutaneous structures are also responsible for the depot formation of the drug in the dermis. CONCLUSION: The patches successfully delivered granisetron hydrochloride by iontophoresis and depot formation was observed in the dermal and subcutaneous structures in the skin.