PharmaSolv - Tips

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Why characterize the phase of the drug substance?

1

Impacts chemical and physical stability

2

Impacts solubility

3

Impacts bioavailability and variability in exposures

4

Impacts formulability

5

Impacts your Intellectual Property (IP)

6

Impacts filing your drug product

Consider prodrugs early in Discovery - Can prodrugs solve your absorption issues?

S.-D. Clas, “The importance of characterizing the crystal form of the drug substance during drug development” invited review, Current Opinions in Drug Delivery (2003), 6(4), 550-560.

M. Palucki et al. "Strategies at the Interface of Drug Discovery and Development: Early Optimization of the Solid State, Phase and Preclinical Toxicology Formulation for Potential Drug Candidates" Journal of Medicinal Chemistry (2010), 53, 5897-5905.

A. Newman, R. Wenslow, “Solid form changes during drug development: good, bad, and ugly case studies”, AAPS Open 2, 2 (2016). doi:10.1186/s41120-016-0003-4

J. Rosenberger, J. Butler, J. Dressman, “A Refined Developability Classification System”, J. Pharm. Sci. 107 (2018), 2020-2032.

Don't forget that defining the sweet spot, balancing both solubility and permeability, is also important to obtaining a successful drug candidate not just selectivity and potency!

A. Dahan, A. Beig, D. Lindley, J.M. Miller, “The Solubility-Permeability Interplay and Oral Drug Formulation Design: Two Heads are Better than One”, Adv. Drug. Del. Rev. 101(2016), 99-107.

I.T. Raheem, A.M. Walji, D. Klein, J. Sanders, D.A. Powell, P. Abeywickrema, G. Barbe, A. Bennet, S.-D. Clas, D. Dubost, M. Embrey, J. Grobler, T.J. Hartingh, D.J. Hazuda, M. Miller, K P. Moore, N. Pajkovic, S. Patel, V. Rada, J.D. Schreier, J. Sisko, T. Steele, J.-F. Truchon, J. Wai, M. Xu, P.J. Coleman, “Discovery of 2-Pyridinone Aminals: A Prodrug Strategy to Advance a Second Generation of HIV-1 Integrase Strand Transfer Inhibitors.”, J. Med. Chem., (2015), 58 (20), 8154–8165.

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