Chapter 18 – Integration of Physical, Chemical, Mechanical, and Biopharmaceutical Properties in Solid Oral Dosage Form Development

Publisher Summary This chapter presents the physico-chemical properties, mechanical properties, and biopharmaceutical properties of drug products, and discusses how this multitude of factors may influence stability, processability, and bioavailability of drug products. As a new chemical entity is identified for development, formulators need to work with chemists to fully characterize physico-chemical properties of the drug substance through a battery of tests. These typically include screening salts and polymorphs, performing accelerated stability studies, generating solubility/dissolution rate data, measuring membrane permeability using Caco-2 cell lines. Once a salt or polymorph is selected for further development, one needs to understand what the target release profile and desired route of delivery is to achieve therapeutic efficacy of the drug candidate. Most pharmaceutical compounds are small organic molecules to be developed as an immediate-release solid oral dosage form. The next step is to select a formulation approach, based on understanding of the biopharmaceutical properties of the drug candidate. Biopharmaceutics Classification System (BCS) class I compounds are highly soluble and highly permeable. As for BCS class II compounds that have high permeability but low aqueous solubility, there are a variety of formulation approaches aimed to enhance solubility and/or dissolution rate of these compounds.