A Semi-mechanistic Modeling Strategy for Characterization of Regional Absorption Properties and Prospective Prediction of Plasma Concentrations Following Administration of New Modified Release Formulations

Abstract

The established model was largely successful in predicting plasma concentration following administration of three newly developed formulations for which no clinical data had been applied during model building.

Meta-analysis of Magnetic Marker Monitoring Data to Characterize the Movement of Single Unit Dosage Forms Though the Gastrointestinal Tract Under Fed and Fasting Conditions

“…The presented model focused only on tablet position. In vivo drug release data have been previously explored: allowing the estimation of regional absorption characteristics along pharmacokinetic data (23,40), or as a reference for in vitroin vivo correlation (30).…”

“…This approach has been superior to a standard absorption model (first-order rate + lag-time) and to a transit compartment model, in the example of extended-release diclofenac data, where no MMM measurement was done. Besides, the model for tablet movement had been connected to an in vitro drug release model and a disposition model in order to predict the pharmacokinetics of a new modified release formulation (40).…”

“…This model-based knowledge can be used as prior information in semi-mechanistic model for drug absorption, involving tablet position. Besides in vitro/in vivo drug release and regional absorption models, this modelbased knowledge on tablet movement can as a part of mechanism based models for drug absorption, be applied for bottom up predictions (40,50) and/or top-down estimation (33).…”

In Vitro and In Vivo Modeling of Hydroxypropyl Methylcellulose (HPMC) Matrix Tablet Erosion Under Fasting and Postprandial Status

“…Such simulations can be used to support of the development process by providing information on the expected typical tablet erosion profiles and the magnitude of variability. If used along with pharmacokinetic data, the model could be extended to predict the variability in the absorption profile of API released from ER formulations (19). It should be noted that the predictive performance of the proposed in vivo HPMC matrix tablet erosion model is appropriate for interpolation but has not been evaluated outside the studied range of covariates.…”

Individualized, discrete event, simulations provide insight into inter- and intra-subject variability of extended-release, drug products

“…It may also be expected that more and more novel research techniques and computational tools will be used to greatly facilitate the in-depth understanding of absorption processes.” Such progress would expand the “personalized medicine” vision to include complicated oral dosage forms [10,12]. Before we can develop methods that provide exploitable explanations of atypical drug absorption profiles, we need means to begin achieving deeper, concrete insight into mechanisms that may underlie intra- and interindividual differences in bioavailability data, including subject-by-formulation interactions [5], when they exist.…”