Investigation of sampling techniques for drug delivery

Abstract

Suitable techniques for monitoring drug delivery are essential for drug screening and determination of proper dosing regimens. Current in vivo dermal sampling techniques are not optimal for drug delivery studies as they are not able to determine true dermal concentrations and do not provide continual sampling in the same skin region. The focus of this research has been to utilize microdialysis sampling for the determination of drug delivery following dermal applications and as a novel in vitro drug transport design.

Initial work focused on an application of microdialysis by determining lidocaine flow around an incision under both passive and iontophoretic conditions in the CD hairless rat. Compared to traditional dermal sampling techniques, cutaneous microdialysis was an ideal technique for this application as it allows continual sampling in site specific regions. The use of iontophoresis on a sutured incision was found to enhance drug flow through the incision.

One of the difficulties with microdialysis is it is limited to the laboratory setting. Ultrafiltration is a promising alternative to microdialysis, as sampling can occur while the animal is freely moving. This study compared dermal microdialysis and ultrafiltration sampling in the Sprague Dawley rat and the Göttingen minipig. The use of cutaneous ultrafiltration sampling was determined to an insufficient sampling technique as it extracted extracellular fluid from both the dermal and subcutaneous regions resulting in delayed drug responses and underestimation of the true drug concentration.

The osmotic pump is a potential alternative to the traditional infusion pump used for microdialysis sampling as it is implanted internally and allows the animal to be freely moving. Overall, the use of an osmotic pump proved to be an effective pumping device for cutaneous microdialysis sampling. Large variations in flow rates were found however the use of an internal standard reduced the variation to an acceptable range.

Finally, an investigation into the use of a new drug transport design that utilizes a cell-coated linear microdialysis probe. Several cell culture parameters including sterilization, substrate coating, and seeding densities were explored. The results from this study suggest that the reliability of this design was insufficient for determining drug penetration.