title: Propagation of uncertainty in nasal spray in vitro performance models using Monte Carlo simulation: Part II. Error propagation during product performance modeling.
abstract: Monte Carlo simulations were applied to investigate the propagation of uncertainty in both input variables and response measurements on model prediction for nasal spray product performance design of experiment (DOE) models in the first part of this study, with an initial assumption that the models perfectly represent the relationship between input variables and the measured responses. In this article, we discard the initial assumption, and extended the Monte Carlo simulation study to examine the influence of both input variable variation and product performance measurement variation on the uncertainty in DOE model coefficients. The Monte Carlo simulations presented in this article illustrate the importance of careful error propagation during product performance modeling. Our results show that the error estimates based on Monte Carlo simulation result in smaller model coefficient standard deviations than those from regression methods. This suggests that the estimated standard deviations from regression may overestimate the uncertainties in the model coefficients. Monte Carlo simulations provide a simple software solution to understand the propagation of uncertainty in complex DOE models so that design space can be specified with statistically meaningful confidence levels.
authors.affiliation: Division of Pharmaceutical Analysis, US Food and Drug Administration, St. Louis, Missouri 63101, USA. changning.guo@fda.hhs.gov
authors.forename: Changning
authors.initials: C
authors.lastname: Guo
authors.forename: William H
authors.initials: WH
authors.lastname: Doub
authors.forename: John F
authors.initials: JF
authors.lastname: Kauffman
mesh_terms: D000281:Administration, Intranasal; D000336:Aerosols / Q000737:chemistry*; D000465:Algorithms; D003198:Computer Simulation; D004339:Drug Compounding; D015195:Drug Design; D008823:Micelles; D015233:Models, Statistical; D009010:Monte Carlo Method; D010316:Particle Size; D012044:Regression Analysis; D012984:Software
chemical_list: D000336:Aerosols; D008823:Micelles