title: Transport mechanisms in oral transmucosal drug delivery: implications for pain management.
abstract: The mechanism for the oral transmucosal delivery of fentanyl citrate (OTFC) was investigated in this work. A developed mathematical model included the following transport characteristics: dissolution of the fentanyl citrate lozenge, diffusion through the saliva and oral mucosal membrane and equilibrium between adjacent layers. An orthogonal-collocation-based solution procedure was adopted to discretize the governing equations and boundary conditions. The Mathematica® built-in function, NDSolve, was applied to integrate the equations with respect to time. Simulations were conducted with a 200 μg-dosage. A novel fabrication method, aimed at maintaining a high flux for a prolonged period of time, was proposed based on the calculated delivery rate and cumulative amount of medicament absorbed into the systemic circulation. The model allows drug manufacturers to decide when to replace the unit based on estimated drug concentrations in the saliva and the mucosal membrane. Both the model and solution strategies were validated using serum fentanyl citrate concentration collected from adult subjects. The predicted profiles, based on parameters obtained from the literature, agree well with the experimental data.
authors.affiliation: Otto H. York Department of Chemical, Biological and Pharmaceutical Engineering, New Jersey Institute of Technology, Newark, NJ 07102, USA.
authors.forename: Kwang Seok
authors.initials: KS
authors.lastname: Kim
authors.forename: Laurent
authors.initials: L
authors.lastname: Simon
mesh_terms: D058956:Administration, Mucosal; D000284:Administration, Oral; D000328:Adult; D000465:Algorithms; D000700:Analgesics / Q000008:administration & dosage* / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D001682:Biological Availability; D001692:Biological Transport / Q000502:physiology; D003198:Computer Simulation; D003692:Delayed-Action Preparations; D004058:Diffusion; D016503:Drug Delivery Systems; D005283:Fentanyl / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D020342:Finite Element Analysis; D006801:Humans; D008954:Models, Biological; D009061:Mouth Mucosa / Q000378:metabolism*; D010146:Pain / Q000188:drug therapy*; D012463:Saliva / Q000378:metabolism
chemical_list: D000700:Analgesics; D003692:Delayed-Action Preparations; D005283:Fentanyl