The Impact of Solubility and Dissolution Assessment on Formulation Strategy and Implications for Oral Drug Disposition

Abstract

This review discusses the importance of drug solid–state properties and of solubility and dissolution measurement for the identification of appropriate formulations/formulation strategies and highlights their impact on drug disposition and candidate selection. Common elements of solubility/dissolution protocols are presented and the methods addressing equilibrium, apparent, kinetic, and intrinsic solubility, as well as powder and intrinsic dissolution are discussed. Tools for drug categorization (BCS, BDDCS) and estimation of oral drug absorption (MAD) are assessed. A detailed description of available formulation approaches is provided, including improvement of drug dissolution rate and/or apparent solubility, drug solubilization approaches, and inhibition of drug precipitation.

Gastrointestinal Delivery of APIs from Chitosan Nanoparticles

“…Drug dissolution, solubility and permeability are the three fundamental parameters used in the Biopharmaceutics Classification System (BCS) to predict the factors limiting drug absorption from GIT [33]. The BCS is recognised as a useful tool for designing drug delivery systems and is adopted by the US Food and Drug Administration (FDA), the European Medicines Agency (EMA) and the World Health Organization (WHO) [34].…”

“…Drug dissolution reflects a dynamic consequence to drug absorption [33], whereby drug is released, dissolved and made accessible for absorption. With the exception of enteric formulations and drugs with low acid solubility, the dissolution process for majority of drugs starts in the stomach where the volume of gastric fluid is sufficient to attain effective drug dissolution [37].…”

Analytical technologies for real-time drug dissolution and precipitation testing on a small scale

“…Miniaturised screening approaches have also been tried for several formulations of poorly soluble drugs [16–18]. Moreover, the impact of miniaturised solubility and dissolution assays on defining the formulation strategy has been excellently summarised by Alsenz [19]…”

“…[16][17][18] Moreover, the impact of miniaturised solubility and dissolution assays on defining the formulation strategy has been excellently summarised by Alsenz. [19] The present work aims to review analytical technologies for small-scale dissolution and precipitation assays. The main focus is on real-time analytics, even though classical offline methods are mentioned as well.…”