Absorption and Drug Development

Second Edition, Wiley, 2012 (ISBN 978-1-1180-5745-2)

Absorption and Drug Development (744 pages) will continue to serve the needs of pharmaceutical R&D as a reference and supplemental textbook on physical property measurement and interpretation (pH, pK_a, log P, log D, solubility, PAMPA, Caco-2/MDCK, and blood-brain barrier permeability). Physical/analytical chemists in pharma companies and at the universities who measure the physical properties of complicated (e.g., practically-insoluble or multiply-ionizable) small molecules, and chemists who synthesize molecules with optimal physical properties and the biologist who apply improved cellular assays to profile these molecules could benefit from the insights provided in the book. Due to its in-depth coverage of fundamental principles and its many property and equation tables, Absorption and Drug Development is expected to be useful resource for some time.

Extensive Data Tables for Computational Chemists

• Unique databases of high-quality measured physicochemical properties, assembled by the author over many years, with many values either determined in the author’s laboratory or extracted out of primary publications, counting
  907 pK_a (many at 37 ^oC)
  346 octanol-water & 116 liposome-water log P
  61 intrinsic solubility
  365 Double-Sink^TM PAMPA
  108 PAMPA-BBB
  195 Caco-2/MDCK (based on averaging of 687 values)
  119 human jejunal permeability (53 compounds)
  602 PS blood-brain barrier permeability-surface
  224 unbound plasma & brain fractions
• Tabulation of many other property results and new solubility equations (61 tables).
• Amply illustrated, with many hand-drawn figures by the author (200 illustrations). 
• Up-to-date (September 2011) references to primary literature (1364 references).
• Mathematical derivations of important physical property equations.

Novel Analysis

The in vitro cellular measurements based on the analysis of permeability in terms of the Dynamic Range Window (transcellular, aqueous boundary layer, and paracellular) biophysical model is unique.  The new flow correction (pH-dependent Crone-Renkin equation) method for in situ brain perfusion can expand the dynamic range of BBB permeability measurements.  The coverage of pK_a determination is perhaps the deepest ever published.  Origin-shifted Yasuda-Shedlovsky and in situ electrode calibration analysis applied to determining ionization constants of practically insoluble molecules is novel. (The author is one of the last standing old-school experts in pK_a analysis.)  The use of cellular biophysical models directly to predict human jejunal permeability is new.  The analysis of solubility is mathematically comprehensive.  The PAMPA coverage is extensive – with several variants discussed in detail.  The Principal has the highest number of PAMPA primary publications of any author.

Educational Resource

Although not specifically designed for the purpose, the book can be used as a supplemental text in graduate courses in preformulation or related physicochemical sciences, with focus on the absorption/distribution part of ADME (absorption, distribution, metabolism, elimination). The book could be used as part of an Advanced Physical Pharmacy and Pharmaceutics course, supplementing and expanding on, for example, Sinko, PJ. Martin’s Physical Pharmacy and Pharmaceutical Sciences. 5^th Ed. Lippincott Williams & Wilkins (2006).

• ‘Getting started’ appendices for processing pK_a and PAMPA data – usefule guides for learning the methods of analysis.
• Book figures are available electronically online at the John Wiley & Sons website.