title: A biorelevant in vitro release/permeation system for oral transmucosal dosage forms.
abstract: 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 C(max) and AUC(0-∞) 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.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298-0581, United States. delvadiapr@vcu.edu
authors.forename: Poonam R
authors.initials: PR
authors.lastname: Delvadia
authors.forename: William H
authors.initials: WH
authors.lastname: Barr
authors.forename: H Thomas
authors.initials: HT
authors.lastname: Karnes
mesh_terms: D000278:Administration, Buccal; D000327:Adsorption; D000328:Adult; D019540:Area Under Curve; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D004058:Diffusion; D004304:Dosage Forms; D004339:Drug Compounding; D004867:Equipment Design; D005240:Feasibility Studies; D006801:Humans; D008567:Membranes, Artificial; D008954:Models, Biological; D009061:Mouth Mucosa / Q000378:metabolism*; D009538:Nicotine / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D010539:Permeability; D015203:Reproducibility of Results; D012463:Saliva / Q000378:metabolism; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000295:instrumentation* / Q000379:methods; D014030:Tobacco, Smokeless / Q000378:metabolism* / Q000493:pharmacokinetics
chemical_list: D004304:Dosage Forms; D008567:Membranes, Artificial; D018722:Nicotinic Agonists; D009538:Nicotine