The Use of Modeling Tools to Drive Efficient Oral Product Design
Journal Title: The AAPS Journal - Year 2012, Vol 14, Issue 3
Abstract
Modeling and simulation of drug dissolution and oral absorption has been increasingly used over the last decade to understand drug behavior in vivo based on the physicochemical properties of Active Pharmaceutical Ingredients (API) and dosage forms. As in silico and in vitro tools become more sophisticated and our knowledge of physiological processes has grown, model simulations can provide a valuable confluence, tying-in in vitro data with in vivo data while offering mechanistic insights into clinical performance. To a formulation scientist, this unveils not just the parameters that are predicted to significantly impact dissolution/absorption, but helps probe explanations around drug product performance and address specific in vivo mechanisms. In formulation, development, in silico dissolution–absorption modeling can be effectively used to guide: API selection (form comparison and particle size properties), influence clinical study design, assess dosage form performance, guide strategy for dosage form design, and breakdown clinically relevant conditions on dosage form performance (pH effect for patients on pH-elevating treatments, and food effect). This minireview describes examples of these applications in guiding product development including those with strategies to mitigate observed clinical exposure liability or mechanistically probe product in vivo performance attributes.
Authors and Affiliations
Neil R. Mathias, John Crison
Keywords
Related Articles
- EP ID EP681247
- DOI 10.1208/s12248-012-9372-3
- Views 60
- Downloads 0
Ligand-Binding Assay Development: What Do You Want to Measure Versus What You Are Measuring?
The analysis of biotherapeutics by ligand-binding assay (LBA) is associated with some unique challenges that are unlike those commonly encountered in chromatographic methods for chemically based small molecule drugs. Whi...
Pharmacokinetic Evaluation of Intranasally Administered Vinyl Polymer-Coated Lorazepam Microparticles in Rabbits
The intranasal (IN) administration of lorazepam is desirable in order to maximize speed of onset and minimise carry-over sedation; however, this benzodiazepine is prone to chemical hydrolysis and poor airway retention, a...
Cloning and characterization of the rat multidrug resistance-associated protein 1
Multidrug resistance-associated protein 1 (MRP1) was originally shown to confer resistance of human tumor cells to a broad range of natural product anticancer drugs. MRP1 has also been shown to mediate efflux transport o...
Challenges and Opportunities in Establishing Scientific and Regulatory Standards for Assuring Therapeutic Equivalence of Modified Release Products: Workshop Summary Report
Modified release products are complex dosage forms designed to release drug in a controlled manner to achieve desired efficacy and safety. Inappropriate control of drug release from such products may result in reduced ef...
Utility of a Bayesian Mathematical Model to Predict the Impact of Immunogenicity on Pharmacokinetics of Therapeutic Proteins
The impact of an anti-drug antibody (ADA) response on pharmacokinetic (PK) of a therapeutic protein (TP) requires an in-depth understanding of both PK parameters and ADA characteristics. The ADA and PK bioanalytical assa...