Overview of Determination of Biopharmaceutical Properties for Development Candidate Selection

Mehran Yazdanian1

1 Pharmaceutical Development, Teva Global R&D, West Chester, Pennsylvania
Publication Name:  Current Protocols in Pharmacology
Unit Number:  Unit 9.17
DOI:  10.1002/0471141755.ph0917s60
Online Posting Date:  March, 2013
GO TO THE FULL TEXT: PDF or HTML at Wiley Online Library


The physicochemical and biopharmaceutical properties of putative drug molecules impact their performance in both in vitro and in vivo studies. The design and selection of molecules with drug‐like properties assists in the selection of drug candidates with a higher probability of success in the development process. Described in this overview are commonly used approaches for measuring compound solubility, permeability, and partitioning in drug discovery and development. The utility of these methods in the drug discovery process and product development is discussed. The evaluation of crystallinity and physicochemical stability in relation to biopharmaceutical properties and in assessing the potential for successful development are also discussed. Curr. Protoc. Pharmacol. 60:9.17.1‐9.17.8. © 2013 by John Wiley & Sons, Inc.

Keywords: biopharmaceutics; solubility; permeability; partitioning

PDF or HTML at Wiley Online Library

Table of Contents

  • Introduction
  • Methodologies
  • Discussion and Summary
  • Literature Cited
  • Tables
PDF or HTML at Wiley Online Library


PDF or HTML at Wiley Online Library



Literature Cited

Literature Cited
   Almarsson, O. and Gardner, C.R. 2003. Novel approaches to issues of developability. Curr. Drug Disc. January 2003:21‐26.
   Artursson, P. and Karlsson, J. 1991. Correlation between oral drug absorption in humans and apparent drug permeability coefficient in human intestinal (Caco‐2) cells. Biochim. Biophys. Res. Commun. 175:880‐885.
   Avdeef A. 2005. The rise of PAMPA. Exp. Opin. Drug Metab. Toxicol. 1:325‐342.
   Comer, J.E.A. 2003. High throughput measurement of logD and pKa. In Drug Bioavailability. Estimation of Solubility, Permeability and Bioavailability (P. Artursson, H. Lennernas, and H. van de Waterbeemd, eds.) pp. 21‐45. Wiley‐VCH, Weinheim, Germany.
   De Angelis, I. and Turco, L. 2011. Caco‐2 cells as a model for intestinal absorption. Curr. Prot. Toxicol. 47:20.6.1‐20.6.15.
   FDA Guidance for Industry, Waiver of In Vivo Bioavailability and Bioequivalence studies for Immediate Release Solid Oral Dosage Forms Based on a Biopharmaceutics Classification System, August 2000, FDA/CDER.
   Galia, E., Nicolaides, E., Horter, D., Lobenberg, R., Reppas, C., and Dressman, J.B. 1998. Evaluation of various dissolution media for predicting in vivo performance of Class I and Class II drugs. Pharm. Res. 15:698‐705.
   Galinis‐Luciani, D., Nguyen, L., and Yazdanian, M. 2007. Is parallel artificial membrane permeability assay a useful tool for discovery? J. Pharm. Sci. 96:2886‐2892.
   Gould, P.L. 1986. Salt selection for basic drugs. Int. J. Pharm. 33:201‐217.
   Guo, J., Elzinga, P.A., Hageman, M.J., and Herron, J.N., 2008. Rapid throughput solubility screening method for BCS class II drugs in animal GI fluids and simulated human GI fluids using a 96 well format. J. Pharm. Sci. 97:1427‐1442.
   Higuchi, T. and Conners, K.A. 1965. Phase solubility techniques. Adv. Anal. Chem. Instrument. 4:117‐212.
   Hodgson, J. 2001. ADMET: Turning chemicals into drugs. Nat. Biotechnol. 19:722‐726.
   Irvine, J., Takahashi, L., Lockhart, K., Cheong, J., Tolan, J. Selick, E., and Grove, R. 1999. MDCK cells: A tool for membrane permeability screening. J. Pharm. Sci. 88:28‐33.
   Kerns, E.H., Di, L., Petusky, S., Farris, M., Ley, R., and Jupp, P. 2004. Combined application of parallel artificial membrane permeability assay and Caco‐2 permeability assays in drug discovery. J. Pharm. Sci. 93:1440‐1453.
   Kola, I. and Landis, J. 2004. Can the pharmaceutical industry reduce attrition rates? Nat. Rev. Drug Disc. 3:711‐715.
   Lennernas, H. 2007. Animal data: The contribution of the Ussing chamber and perfusion systems to predicting human oral drug delivery in vivo. Adv. Drug Deliv. Rev. 59:1103‐1120.
   Leo, A., Hensch, C., and Elkins, D. 1971. Partition coefficients and their uses. Chem. Rev. 71:525‐615.
   Lipinski, C.A., Lombardo, F., Dominy, B.W., and Feeney, P.J. 2001. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Del. Rev. 46:3‐26.
   Lipinski, C. 2003. Aqueous solubility in discovery, chemistry, and assay changes. In Drug Bioavailability: Estimation of Solubility, Permeability, Absorption and Bioavailability (H. van de Waterbeemd, H. Lennernäs, and P. Artursson, eds.) pp. 215‐231. Wiley‐VCH, Weinheim, Germany.
   Mannhold, R., Poda, G.I., Ostermann, C., and Tetko, I.V. 2009. Calculation of molecular lipophilicity: State‐of‐the‐art and comparison of log P methods on more than 96,000 compounds. J. Pharm. Sci. 98:861‐893.
   Remington, J.R. 1995. Remington: The Science and Practice of Pharmacy. (Gennaro, A.R., ed.) pp. 196‐212. Mack Publishing, Easton, Penn.
   Sugano, K., Nabuchi, Y., Machida, M., and Aso, Y. 2003. Prediction of human intestinal permeability using artificial membrane permeability. Int. J. Pharm. 257:245‐251.
   Tang, F., Horie, K., and Borchardt, R.T. 2002. Are MDCK cells transfected with the human MDR1 gene a good model of the human intestinal mucosa? Pharm. Res. 19:765‐772.
   USP34‐NF29 2011. United States Pharmacopeia—National Formulary, Description and Solubility. p. 994.
   Veber, D.F., Johnson, S.R., Cheng H‐Y. Smith, B.R., Ward, K.W., and Kopple, K.D. 2002. Molecular properties that influence the oral bioavailability of drug candidates, J. Med. Chem. 45:2615‐2623.
   Yazdanian, M., Glynn, S.L., Wright, J.L., and Hawi, A. 1998. Correlating partitioning and Caco‐2 cell permeability of structurally diverse small molecular weight compounds. Pharm Res. 15:1490‐1494.
PDF or HTML at Wiley Online Library