CR White Paper* on pH-solubility diagrams
written by Dan Lundberg and Stefan Ulvenlund 2017
pH-Solubility diagrams and their usefulness in characterization of salts of poorly soluble drug substances
Introduction
Since the true solubility of a substance is always limited by the solubility of the most stable form at a certain set of conditions, careless use of salt forms of drug substances may result in unwanted situations. In order to avoid unpleasant surprises, care should be taken to identify the species and equilibria that influence the effective solubility of an API in a relevant range of conditions. In this paper, the construction of proper solubility diagrams is discussed. We begin with a look at the simple case of a monoprotic base with a non-titrating counterion, then continue with a brief discussion on the sometimes substantial influence of background salt, and finish off by considering the solubility of salts carrying a titrating counterion. There are sometimes good reasons for using a salt of an active compound, however, there are also reasons to be cautious…
* a White Paper is according to Wikipedia “… an authoritative report or guide that informs readers concisely about a complex issue and presents the issuing body’s philosophy on the matter. It is meant to help readers understand an issue, solve a problem, or make a decision.” Exactly what we aim with all we do!
