A biorelevant in vitro release/permeation system for oral transmucosal dosage forms

This research describes the development and validation of a biorelevant in vitro release/permeation system to predict the in vivo performance of oral transmucosal dosage forms. The system is a biorelevant bidirectional transmucosal apparatus which allows better simulation of oral cavity physiological variables in comparison to compendial dissolution apparatuses and therefore may be a better predictor of in vivo behavior. The feasibility of the bidirectional apparatus was studied using smokeless tobacco (snus) as a model oral transmucosal product. In this research, nicotine release and permeation was investigated from commercially available snus using a modified USP IV flow-through apparatus, a commercially available vertical diffusion cell and a fabricated novel bidirectional transmucosal apparatus. The percent nicotine released/permeated was utilized as an input function for the prediction of in vivo plasma nicotine profiles by back calculation based on the Wagner–Nelson method. The prediction errors in Cmax and AUC0–∞ with the USP IV flow-through device, vertical diffusion cell and novel apparatus were 4.03, 22.85 and 1.59 and −5.85, 5.85 and −9.27% respectively. This work demonstrated the suitability of the novel bidirectional transmucosal apparatus for predicting the in vivo behavior of oral transmucosal products.

Figure optionsDownload high-quality image (154 K)Download as PowerPoint slide