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 66
- Downloads 0
Reproductible production of a PEGylated dual-acting peptide for diabetes
A pEGylated glucagon-like peptide-1 (GLP-1) agonist and glucagon antagonist hybrid peptide was engineered as a potential treatment for type 2 diabetes. To support preclinical development of this PEGylated dual-acting pep...
Biological Products for the Treatment of Psoriasis: Therapeutic Targets, Pharmacodynamics and Disease-Drug-Drug Interaction Implications
Psoriasis is a chronic inflammatory skin disease condition that involves altered expression of a broad spectrum of proinflammatory cytokines which are associated with activation of T cells and proliferation of keratinocy...
The pharmacokinetics of escitalopram in patients with hepatic impairment
The effect of hepatic impairment on the pharmacokinetics of escitalopram was determined by means of nonlinear mixed effect modeling, considering both the Child-Pugh classification (and its components) and cytochrome P450...
The Challenges of Assessing Osteoarthritis and Postoperative Pain in Dogs
The challenge of measuring pain in veterinary medicine is compounded by the lack of fully validated, reliable methods to measure and assess pain in nonverbal patients. In human medicine, there are numerous, validated pai...
A Bayesian Approach for Quantifying Trace Amounts of Antibody Aggregates by Sedimentation Velocity Analytical Ultracentrifugation
Sedimentation velocity analytical ultracentrifugation (SV-AUC) has become an important tool for the characterization of the purity of protein therapeutics. The work presented here addresses a need for methods orthogonal...