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Assessment of Nasal Drug Delivery in Humans Using Radionuclide Imaging Techniques
Wednesday, November 14
7:00 am – 8:15 am
Sunrise Session
ACPE #073-999-07-553-L04
In recent years growing interest has focused on the use of the nasal route for systemic delivery and brain targeting, as well as for compounds which impact local pharmacological effects. In this respect, an understanding of the deposition residence time and clearance of nasal drug formulations from the human nasal cavity is important in order to optimally exploit the nasal route for delivery of drugs. Nasal drug delivery may be assessed by a variety of means, but high reliance is often placed upon in vitro testing methodologies to determine parameters such as emitted dose, droplet or particle size distribution, spray patterns, and plume geometry. However, these methods fail to provide information on the residence time of the drug in the nasal cavity and the extent of the amount of drug that is eliminated from the nasal cavity. Current Food and Drug Administration (FDA) guidance recommends these in vitro methods as means of documenting bioavailability (BA) and bioequivalence (BE) for topically acting solution formulations, because they can be performed reproducibly and are more discriminating among comparable products. Furthermore, the FDA recently released draft guidance procedures for the pharmaceutical industry regarding BA and BE studies for locally acting nasal aerosols and nasal sprays. Although the FDA draft proposed that BA/BE be determined primarily using in vitro methods, the draft also mentioned imaging as a potential means for in vivo measurements. Non-invasive imaging techniques can measure local bioavailability of a drug at the site of action in the nasal cavity, and the nasal deposition data obtained can be strongly correlated with clinical response to such drugs. For assessing the bioequivalence of nasal drugs, radionuclide imaging methods can determine in vivo drug delivery more precisely than can in vitro testing, and this former methodology is more incisive than clinical response studies. In addition, the approach requires fewer patients than clinical response studies, providing reliable data in less time and enabling accurate determination of the bioavailability of nasal products. Furthermore, it can demonstrate the bioadhesive properties of novel formulations in the nasal cavity and can provide information on the extent of drug penetration into the lungs and other tissues. In addition, by quantitative analysis of deposition and clearance of drug formulations, radionuclide imaging studies will allow a comparison to be made between the performance of new nasal drug delivery systems and those already marketed. For these reasons, imaging methodologies can play a key role in the regulatory approval process for new nasal products, helping to facilitate the early introduction of these products to the market.
Moderator
Abeer M. Al-Ghananeem, Ph.D.
University of Kentucky
Recent Advances in Drug Formulation Assessment by Gamma Scintigraphy
Erik Sandefer, Ph.D.
Scintipharma Inc.
Radionuclide Imaging: Establishing Bioequivalence Between Nasal Products
George A. Digenis, Ph.D.
University of Kentucky
