Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8994350 | Journal of Pharmaceutical Sciences | 2005 | 16 Pages |
Abstract
Solubility is one of the most important parameters for lead selection and optimization during drug discovery. Its determination should therefore take place as early as possible in the process. Because of the large numbers of compounds involved and the very low amounts of each compound available in the early development stage, it is highly desirable to measure the solubility with as little compound as possible and to be able to improve the throughput of the methods used. In this work, a miniaturized shakeâflask method was developed and the solubility results were compared with those measured by semiautomated potentiometric acid/base titrations and computational methods for 21 poorly soluble compounds with solubilities mostly in the range 0.03-30 μg/mL. The potentiometric method is very economical (approximately 100 μg of a poorly soluble compound is needed) and is able to create a pH/solubility profile with one single determination, but is limited to ionizable compounds. The miniaturized shakeâflask method can be used for all compounds and a wide variety of media. Its precision and throughput proved superior to the potentiometric method for very poorly soluble compounds. Up to 20 compounds a week can be studied with one setâup. Calculated solubility data seem to be sufficient for a first estimate of the solubility, but they cannot currently be used as a substitute for experimental measurements at key decision points in the development process. © 2004 WileyâLiss, Inc. and the American Pharmacists Association J Pharm Sci 94:1-16, 2005
Keywords
Related Topics
Health Sciences
Pharmacology, Toxicology and Pharmaceutical Science
Drug Discovery
Authors
A. Glomme, J. März, J.B. Dressman,